Management of depression

From Wikipedia, the free encyclopedia

Management of depression is the treatment of depression that may involve a number of different therapies: medications, behavior therapy, psychotherapy, and medical devices.

Depression is a symptom of some physical diseases; a side effect of some drugs and medical treatments; and a symptom of some mood disorders such as major depressive disorder or dysthymia. Physical causes are ruled out with a clinical assessment of depression that measures vitamins, minerals, electrolytes, and hormones.

Though psychiatric medication is the most frequently prescribed therapy for major depression, psychotherapy may be effective, either alone or in combination with medication. Combining psychotherapy and antidepressants may provide a "slight advantage", but antidepressants alone or psychotherapy alone are not significantly different from other treatments, like "active intervention controls". ( e.g., sham acupuncture) Given an accurate diagnosis of major depressive disorder, in general the type of treatment (psychotherapy and/or antidepressants, alternate or other treatments, or active intervention) is "less important than getting depressed patients involved in an active therapeutic program."

Psychotherapy is the treatment of choice in those under the age of 18, with medication offered only in conjunction with the former and generally not as a first line agent. The possibility of depression, substance misuse or other mental health problems in the parents should be considered and, if present and if it may help the child, the parent should be treated in parallel with the child.

Psychotherapy and behavior therapy

Main article: Psychotherapy

There are a number of different psychotherapies for depression which are provided to individuals or groups by psychotherapists, psychiatrists, psychologists, clinical social workers, counselors or psychiatric nurses. With more chronic forms of depression, the most effective treatment is often considered to be a combination of medication and psychotherapy. Psychotherapy is the treatment of choice in people under 18. A meta-analysis examined the effectiveness of psychotherapy for depression across ages from younger than 13 years to older than 75 years. It summarizes results from 366 trials included 36,702 patients. It found that the best results were for young adults, with an average effect size of g=.98 (95% CI, 0.79-1.16). The effects were smallest for young children (<13 years), g = .35 (95% CI, 0.15-0.55), and second largest in the oldest group, g = .97 (95% CI, 0.42-1.52). The study was not able to compare the different types of therapy to each other. Most of the studies with children used therapies originally developed with adults, which may have reduced the effectiveness. The greater benefits with young adults might be due to a large number of studies including college students, who might have an easier time learning therapy skills and techniques. Most of the studies in children were done in the US, whereas in older age groups, more balanced numbers of studies came from Europe and other parts of the world as well.

As the most studied form of psychotherapy for depression, cognitive behavioral therapy (CBT) is thought to work by teaching clients to learn a set of cognitive and behavioral skills, which they can employ on their own. Earlier research suggested that cognitive behavioral therapy was not as effective as antidepressant medication in the treatment of depression; however, more recent research suggests that it can perform as well as antidepressants in treating patients with moderate to severe depression. Beck's treatment manual, Cognitive therapy of depression, has undergone the most research and accumulated the most evidence for its use. However, a number of other CBT manuals also have evidence to support their effectiveness with depression.

The effect of psychotherapy on patient and clinician rated improvement as well as on revision rates have declined steadily from the 1970s.

A systematic review of data comparing low-intensity CBT (such as guided self-help by means of written materials and limited professional support, and website-based interventions) with usual care found that patients who initially had more severe depression benefited from low-intensity interventions at least as much as less-depressed patients.

For the treatment of adolescent depression, one published study found that CBT without medication performed no better than a placebo, and significantly worse than the antidepressant fluoxetine. However, the same article reported that CBT and fluoxetine outperformed treatment with only fluoxetine. Combining fluoxetine with CBT appeared to bring no additional benefit in two different studies or, at the most, only marginal benefit, in a fourth study.

Behavior therapy for depression is sometimes referred to as behavioral activation. In addition, behavioral activation appears to take less time and lead to longer lasting change. Two well-researched treatment manuals include Social skills training for depression and Behavioral activation treatment for depression.

Emotionally focused therapy, founded by Sue Johnson and Les Greenberg in 1985, treats depression by identifying and processing underlying emotions. The treatment manual, Facilitating emotional change, outlines treatment techniques.

Acceptance and commitment therapy (ACT), a mindfulness form of CBT, which has its roots in behavior analysis, also demonstrates that it is effective in treating depression, and can be more helpful than traditional CBT, especially where depression is accompanied by anxiety and where it is resistant to traditional CBT.

A review of four studies on the effectiveness of mindfulness-based cognitive therapy (MBCT), a recently developed class-based program designed to prevent relapse, suggests that MBCT may have an additive effect when provided with the usual care in patients who have had three or more depressive episodes, although the usual care did not include antidepressant treatment or any psychotherapy, and the improvement observed may have reflected non-specific or placebo effects. Of note, although Mindfulness-based cognitive therapy for depression prevented relapse of future depressive episodes, there is no research on whether it can cause the remission of a current depressive episode.

Interpersonal psychotherapy (IPT) focuses on the social and interpersonal triggers that may cause depression. There is evidence that it is an effective treatment for depression. Here, the therapy takes a fairly structured course (often 12 sessions, as in the original research versions) as in the case with CBT; however, the focus is on relationships with others. Unlike family therapy, IPT is an individual format, so it is possible to work on interpersonal themes even if other family members do not come to the session. Therapy can be used to help a person develop or improve interpersonal skills in order to allow him or her to communicate more effectively and reduce stress. In a meta-analysis of 16 studies and 4,356 patients, the average improvement in depressive symptoms was an effect size of d = 0.63 (95% CI, 0.36 to 0.90). IPT combined with pharmacotherapy was more effective in preventing relapse than pharmacotherapy alone, number needed to treat = 7.63.

Psychoanalysis, a school of thought founded by Sigmund Freud that emphasizes the resolution of unconscious mental conflicts, is used by its practitioners to treat clients presenting with major depression. A more widely practiced technique, called psychodynamic psychotherapy, is loosely based on psychoanalysis and has an additional social and interpersonal focus. In a meta-analysis of three controlled trials, psychodynamic psychotherapy was found to be as effective as medication for mild to moderate depression.

Shared care

Shared decision making is an approach whereby patients and clinicians freely share important evidence when tasked with decision making and where patients are guided to consider the best available options to make an informed decision. The principles are well documented, but there is a gap in that it's hard to apply them in routine clinical practice. The steps have been simplified into five steps. The first step is seeking patient participation in that the health practitioner is tasked with communicating existing choices and therefore inviting them to the decision-making process. The next step involves assisting the patient to explore and compare the treatment options by a critical analysis of the risks and benefits. The third step involves the assessment of the patient's values and what they prefer taking to account what is of paramount urgency to the patient. Step 4 involves decision making where the patient and the practitioner make a conclusive decision on the best option and arrange for subsequent follow up meetings. Finally, the fifth step involves the analysis of the patient's decision'. Five steps for you and your patients to work together to make the best possible health care decisions. The step involves monitoring of the degree of implementation, overcoming of barriers of decision implantation consequently the decisions need to be revisited and optimized thus ensuring the decision has a positive impact on health outcomes. Its success relies on the ability of the health practitioner to create a good interpersonal relationship with the patient. (Stone, 2017)

Depression is a major problem globally, affecting an estimated 4.4 percent of the world population in 2017, roughly equivalent to 300 million people. The depression is multifactorial and has been on the increase due to societal pressure, genetic association and increase in use of drugs (Zhang et al. 2016). incorporation of nursing in management of depression may seem important in that nursing hold a pivotal role in health care delivery where they are they are the health practitioners that have been trained to be versatile from clinical to psychological care Their incorporation shared decision making in treating depression may be important as nurses are known to have the best interpersonal relationship with the patients thus a better collaborative model can be achieved due to this fact (Williams et al. 2016). With this in mind, the nurses may serve to administer drugs in management, prepare and maintain the patient's records, interaction with other care staff to achieve optimum care, and organizing therapy sessions (Lu et al. 2019).

Kathleen Walsh, 2017, recognizes that Dr. Velligan stated that SDM is of importance in demonstrating patient preferences in decision making when there is no clear approach to treatment. In addition, numerous tools can be used to make the decision making the process easier these include the Controlled Preferences Scale that informs clinicians on how to actively involve patients. She further gives the suggestion that providers need to embrace shared decision making by making sure the patients participate actively in their management thus enabling the success of the model.

Medication

See also: List of antidepressants

To find the most effective pharmaceutical drug treatment, the dosages of medications must often be adjusted, different combinations of antidepressants tried, or antidepressants changed.

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft, Lustral), escitalopram (Lexapro, Cipralex), fluoxetine (Prozac), paroxetine (Seroxat), and citalopram, are the primary medications considered, due to their relatively mild side effects and broad effect on the symptoms of depression and anxiety, as well as reduced risk in overdose, compared to their older tricyclic alternatives. Those who do not respond to the first SSRI tried can be switched to another. If sexual dysfunction is present prior to the onset of depression, SSRIs should be avoided. Another popular option is to switch to the atypical antidepressant bupropion (Wellbutrin) or to add bupropion to the existing therapy; this strategy is possibly more effective. It is not uncommon for SSRIs to cause or worsen insomnia; the sedating noradrenergic and specific serotonergic antidepressant (NaSSA) antidepressant mirtazapine (Zispin, Remeron) can be used in such cases.

For children and adolescents with moderate-to-severe depressive disorder, fluoxetine seems to be the best treatment (either with or without cognitive behavioural therapy) but more research is needed to be certain. Sertraline, escitalopram, duloxetine might also help in reducing symptoms. In the UK fluoxetine and escitalopram are the only antidepressants recommended for people under the age of 18, though, if a child or adolescent patient is intolerant to fluoxetine, another SSRI may be considered.

Evidence of effectiveness of SSRIs in those with depression complicated by dementia is lacking.

Norepinephrine dopamine reuptake inhibitor

Some norepinephrine–dopamine reuptake inhibitors can be used as antidepressants.

Norepinephrine reuptake inhibitor

Norepinephrine reuptake inhibitors (NRIs) can be used as antidepressants.

Serotonin norepinephrine reuptake inhibitor

Venlafaxine (Effexor) from the SNRI class may be moderately more effective than SSRIs; however, it is not recommended as a first-line treatment because of the higher rate of side effects, and its use is specifically discouraged in children and adolescents.

Tricyclic antidepressant

Tricyclic antidepressants (TCAs) have more side effects than SSRIs and are usually reserved for the treatment of inpatients, for whom the tricyclic antidepressant amitriptyline, in particular, appears to be more effective.

Monoamine oxidase inhibitor

Monoamine oxidase inhibitors, have historically been plagued by questionable efficacy (although early studies used dosages now considered too low) and life-threatening adverse effects. They are still used only rarely, although newer agents of this class (RIMA), with a better side effect profile, have been developed.

In older patients TCAs and SSRIs are of the same efficacy. However, there are differences between TCA related antidepressants and classical TCAs in terms of side effect profiles and withdrawal when compared to SSRIs.

There is evidence a prominent side-effect of antidepressants, emotional blunting, is confused with a symptom of depression itself. The cited study, according to Professor Linda Gask was:

'funded by a pharmaceutical company (Servier) and two of its authors are employees of that company', which may bias the results. The study authors' note: "emotional blunting is reported by nearly half of depressed patients on antidepressants and that it appears to be common to all monoaminergic antidepressants not only SSRIs". Additionally, they note: "The OQuESA scores are highly correlated with the HAD depression score; emotional blunting cannot be described simply as a side-effect of antidepressant, but also as a symptom of depression. More emotional blunting is associated with a poorer quality of remission.

NMDA antagonists

See also: NMDA receptor antagonist

Ketamine

Research on the antidepressant effects of ketamine infusions at subanaesthetic doses has consistently shown rapid (4 to 72 hours) responses from single doses, with substantial improvement in mood in the majority of patients and remission in some. However, these effects are often short-lived, and attempts to prolong the antidepressant effect with repeated doses and extended ("maintenance") treatment have resulted in only modest success. A nasal spray formulation of esketamine, sold under the brand name Spravato, gained FDA approval in 2019 for the treatment of treatment-resistant depression when combined with an oral antidepressant.

Zinc

A 2012 cross-sectional study found an association between zinc deficiency and depressive symptoms among women, but not men, and a 2013 meta-analysis of 17 observational studies found that blood zinc concentrations were lower in depressed subjects than in control subjects. A 2012 meta-analysis found that zinc supplementation as an adjunct to antidepressant drug treatment significantly lowered depressive symptom scores of depressed patients. The potential mechanisms underlying the association between low serum zinc and depression remain unclear, but may involve the regulation of neurotransmitter, endocrine and neurogenesis pathways. Zinc supplementation has been reported to improve symptoms of ADHD and depression. A 2013 review found that zinc supplementation may be an effective treatment in major depression.

Acetyl-l-carnitine

Acetylcarnitine levels were lower in depressed patients than controls and in rats it causes rapid antidepressant effects through epigenetic mechanisms. A systematic review and meta-analysis of 12 randomized controlled trials found "supplementation significantly decreases depressive symptoms compared with placebo/no intervention, while offering a comparable effect with that of established antidepressant agents with fewer adverse effects."

Augmentation

Physicians often add a medication with a different mode of action to bolster the effect of an antidepressant in cases of treatment resistance; a 2002 large community study of 244,859 depressed Veterans Administration patients found that 22% had received a second agent, most commonly a second antidepressant. Stephen M. Stahl, renowned academician in psychopharmacology, has stated resorting to a dynamic psychostimulant, in particular, d-amphetamine is the "classical augmentation strategy for treatment-refractory depression". However, the use of stimulants in cases of treatment-resistant depression is relatively controversial.

It is also possible to use a benzodiazepine as to improve sleep without impairing the antidepressant response specially in patients presenting symptoms of insomnia and disturbed sleep. A randomized controlled trial found that the use of eszopiclone with fluoxetine resulted in a better remission rate.

Addition of atypical antipsychotics when the patient has not responded to an antidepressant is also known to increase the effectiveness of antidepressant drugs, albeit at the cost of more frequent and potentially serious side effects.

Lithium

Lithium has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. Furthermore, lithium dramatically decreases the suicide risk in recurrent depression. According to the results of the STAR-D experiment, the remission rate of lithium for treatment-resistant depression is about 15.9%.

Thyroid hormones

There is some evidence for the addition of a thyroid hormone, triiodothyronine, in patients with normal thyroid function.

For TRD patients, T3 has been studied in the STAR-D study with having a remission rate of 24.7%. T4 is also being studied for this purpose and found remission rates of 21.5% - 64.7% for TRD patients.

Efficacy of medication and psychotherapy

Antidepressants are statistically superior to placebo but their overall effect is low-to-moderate. In that respect they often did not exceed the National Institute for Health and Clinical Excellence criteria for a "clinically significant" effect. In particular, the effect size was very small for moderate depression but increased with severity, reaching "clinical significance" for very severe depression. These results were consistent with the earlier clinical studies in which only patients with severe depression benefited from either psychotherapy or treatment with an antidepressant, imipramine, more than from the placebo treatment. Despite obtaining similar results, the authors argued about their interpretation. One author concluded that there "seems little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide benefit." The other author agreed that "antidepressant 'glass' is far from full" but disagreed "that it is completely empty". He pointed out that the first-line alternative to medication is psychotherapy, which does not have superior efficacy.

Antidepressants in general are as effective as psychotherapy for major depression, and this conclusion holds true for both severe and mild forms of MDD. In contrast, medication gives better results for dysthymia. The subgroup of SSRIs may be slightly more efficacious than psychotherapy. On the other hand, significantly more patients drop off from the antidepressant treatment than from psychotherapy, likely because of the side effects of antidepressants. Successful psychotherapy appears to prevent the recurrence of depression even after it has been terminated or replaced by occasional "booster" sessions. The same degree of prevention can be achieved by continuing antidepressant treatment.

Two studies suggest that the combination of psychotherapy and medication is the most effective way to treat depression in adolescents. Both TADS (Treatment of Adolescents with Depression Study) and TORDIA (Treatment of Resistant Depression in Adolescents) showed very similar results. TADS resulted in 71% of their teen subjects having "much" or "very much" improvement in mood over the 61% with medication alone and 43% with CBT alone. Similarly, TORDIA showed a 55% improvement with CBT and drugs versus a 41% with drug therapy alone. However, a more recent meta-analysis of 34 trials of 14 drugs used with children and adolescents found that only fluoxetine produced significant benefit compared to placebo, with a medium-sized effect (standardize mean difference = .5).

Treatment resistance

The risk factors for treatment resistant depression are: the duration of the episode of depression, severity of the episode, if bipolar, lack of improvement in symptoms within the first couple of treatment weeks, anxious or avoidant and borderline comorbidity and old age. Treatment resistant depression is best handled with a combination of conventional antidepressant together with atypical antipsychotics. Another approach is to try different antidepressants. It's inconclusive which approach is superior. Treatment resistant depression can be misdiagnosed if subtherapeutic doses of antidepressants is the case, patient nonadherence, intolerable adverse effects or their thyroid disease or other conditions is misdiagnosed as depression.

Experimental treatments

Ayahuasca

Research into ayahuasca has been recommended, given there is limited early evidence of potential antidepressant and anxiolytic effects.

Chromium

Clinical and experimental studies have reported antidepressant activity of chromium particularly in atypical depression, characterized by increased appetite and carbohydrate craving.

Creatine

The amino acid creatine, commonly used as a supplement to improve the performance of bodybuilders, has been studied for its potential antidepressant properties. A review found that creatine "has the potential to improve these disruptions [of brain metabolism] in some patients, and early clinical trials indicate that it may have efficacy as an antidepressant agent." Studies on mice have found that the antidepressant effects of creatine can be blocked by dopamine receptor antagonists such as haloperidol, suggesting that the drug acts on dopamine pathways.

Inositol

Inositol, a sugar alcohol in fruits, beans, grains and nuts, was found to be significantly better than placebo in treating depression in a double-blind, controlled trial.  It was also reported to be reduced in human CSF in depression and found to lead to “major improvement” in 9 of 11 depressed patients in an open label trial. 

Magnesium

A meta-analysis has found an association between magnesium intake and depression. Magnesium was lower in serum of depressed patients than controls.

A 2018 review found that Mg²⁺ supplementation (range 225–4000 mg) and number of weeks of treatment (range 1–12) were not related to changes in mood disorder.

Essential Fatty Acids

There is insufficient evidence to determine that omega-3 fatty acid has any effect on depression. A 2016 review found that if trials with formulations containing mostly eicosapentaenoic acid (EPA) are separated from trials using formulations containing docosahexaenoic acid (DHA), it appeared that EPA may have an effect while DHA may not, but there was insufficient evidence to be sure.

A 2020 meta-analysis showed that a high dose of omega-3 polyunsaturated fatty acid (>2g/day) used as an adjuvent improved depressive symptoms.

Dopamine receptor agonist

Some research suggests dopamine receptor agonists, most commonly pramipexole, may be effective in treating depression. Studies are few and results are preliminary, however.

N-Acetylcysteine

A systematic review and meta-analysis of 5 studies found that N-acetylcysteine reduces depressive symptoms more than placebo and has good tolerability. N-acetylecysteine may exert its benefits by replenishing the chief cellular antioxidant, glutathione, thus modulating glutamatergic, neurotropic and inflammatory pathways.

Psilocybin

Psilocybin has been shown in several studies to improve symptoms in people with treatment-resistant depression. In 2018 and 2019, the FDA designated psilocybin as a "breakthrough therapy" for drug-resistant depression and major depressive disorder.

St John's wort

Main article: St John's wort

A 2008 Cochrane Collaboration meta-analysis concluded that "The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation." The United States National Center for Complementary and Integrative Health advice is that "St. John's wort may help some types of depression, similar to treatment with standard prescription antidepressants, but the evidence is not definitive." and warns that "Combining St. John's wort with certain antidepressants can lead to a potentially life-threatening increase of serotonin, a brain chemical targeted by antidepressants. St. John's wort can also limit the effectiveness of many prescription medicines."

Rhodiola rosea

A 2011 review reported Rhodiola rosea "is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects."

Saffron

A 2013 meta-analysis found that saffron supplementation significantly reduced depression symptoms compared to placebo, and both saffron supplementation and the antidepressant groups were similarly effective in reducing depression symptoms. A 2015 meta-analysis supported the "efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior." Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations.

SAMe

S-Adenosyl methionine (SAMe) is available as a prescription antidepressant in Europe and an over-the-counter dietary supplement in the US. Evidence from 16 clinical trials with a small number of subjects, reviewed in 1994 and 1996 suggested it to be more effective than placebo and as effective as standard antidepressant medication for the treatment of major depression.

Tryptophan and 5-HTP

The amino acid tryptophan is converted into 5-hydroxytryptophan (5-HTP) which is subsequently converted into the neurotransmitter serotonin. Since serotonin deficiency has been recognized as a possible cause of depression, it has been suggested that consumption of tryptophan or 5-HTP may therefore improve depression symptoms by increasing the level of serotonin in the brain. 5-HTP and tryptophan are sold over the counter in North America, but requires a prescription in Europe. The use of 5-HTP instead of tryptophan bypasses the conversion of tryptophan into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin, and 5-HTP easily crosses the blood–brain barrier unlike tryptophan, which requires a transporter.

Small studies have been performed using 5-HTP and tryptophan as adjunctive therapy in addition to standard treatment for depression. While some studies had positive results, they were criticized for having methodological flaws, and a more recent study did not find sustained benefit from their use. The safety of these medications has not been well studied. Due to the lack of high quality studies, preliminary nature of studies showing effectiveness, the lack of adequate study on their safety, and reports of Eosinophilia–myalgia syndrome from contaminated tryptophan in 1989 and 1990, the use of tryptophan and 5-HTP is not highly recommended or thought to be clinically useful.

Medical devices

A variety of medical devices are in use or under consideration for treatment of depression including devices that offer electroconvulsive therapy, vagus nerve stimulation, repetitive transcranial magnetic stimulation, and cranial electrotherapy stimulation. The use of such devices in the United States requires approval by the U.S. Food and Drug Administration (FDA) after field trials. In 2010 an FDA advisory panel considered the question of how such field trials should be managed. Factors considered were whether drugs had been effective, how many different drugs had been tried, and what tolerance for suicides should be in field trials.

Electroconvulsive therapy

Main article: Electroconvulsive therapy

In 2004, a meta-analytic review paper found in terms of efficacy, "a significant superiority of ECT in all comparisons: ECT versus simulated ECT, ECT versus placebo, ECT versus antidepressants in general, ECT versus tricyclics and ECT versus monoamine oxidase inhibitors."

Electroconvulsive therapy (ECT) is a standard psychiatric treatment in which seizures are electrically induced in patients to provide relief from psychiatric illnesses. ECT is used with informed consent as a last line of intervention for major depressive disorder. Among the elderly, who often experience depression, the efficacy of ECT is difficult to determine due to the lack of trials comparing ECT to other treatments.

A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or bipolar. Follow-up treatment is still poorly studied, but about half of people who respond relapse with twelve months.

Aside from effects in the brain, the general physical risks of ECT are similar to those of brief general anesthesia. Immediately following treatment, the most common adverse effects are confusion and memory loss. ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.

A usual course of ECT involves multiple administrations, typically given two or three times per week until the patient no longer has symptoms ECT is administered under anesthetic with a muscle relaxant. Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some patients receive maintenance ECT.

ECT appears to work in the short term via an anticonvulsant effect mostly in the frontal lobes, and longer term via neurotrophic effects primarily in the medial temporal lobe.

Deep brain stimulation

The support for the use of deep brain stimulation in treatment-resistant depression comes from a handful of case studies, and this treatment is still in a very early investigational stage. In this technique electrodes are implanted in a specific region of the brain, which is then continuously stimulated. A March 2010 systematic review found that "about half the patients did show dramatic improvement" and that adverse events were "generally trivial" given the younger psychiatric patient population than with movements disorders. Deep brain stimulation is available on an experimental basis only in the United States; no systems are approved by the FDA for this use.

Repetitive transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) or deep transcranial magnetic stimulation is a noninvasive method used to stimulate small regions of the brain. During a TMS procedure, a magnetic field generator, or "coil" is placed near the head of the person receiving the treatment. The coil produces small electric currents in the region of the brain just under the coil via electromagnetic induction. The coil is connected to a pulse generator, or stimulator, that delivers electric current to the coil.

TMS was approved by the FDA for treatment-resistant major depressive disorder in 2008 and as of 2014 clinical evidence supports this use. The American Psychiatric Association, the Canadian Network for Mood and Anxiety Disorders, and the Royal Australia and New Zealand College of Psychiatrists have endorsed rTMS for trMDD.

The response rate is about 29% for TRD patients. Remission rate is about 20%.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) uses an implanted electrode and generator to deliver electrical pulses to the vagus nerve, one of the primary nerves emanating from the brain. It is an approved therapy for treatment-resistant depression in the EU and US and is sometimes used as an adjunct to existing antidepressant treatment. The support for this method comes mainly from open-label trials, which indicate that several months may be required to see a benefit. The only large double-blind trial conducted lasted only 10 weeks and yielded inconclusive results; VNS failed to show superiority over a sham treatment on the primary efficacy outcome, but the results were more favorable for one of the secondary outcomes. The authors concluded "This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression."

Cranial electrotherapy stimulation

A 2014 Cochrane review found insufficient evidence to determine whether or not Cranial electrotherapy stimulation with alternating current is safe and effective for treating depression.

Transcranial direct current stimulation

A 2016 meta-analysis of transcranial direct current stimulation (tDCS) reported some efficacy of tDCS in the treatment of acute depressive disorder with moderate effect size, and low efficacy in treatment-resistant depression, and that use of 2 mA current strength over 20 min per day over a short time span can be considered safe.

Other treatments

Herbal remedies

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder. Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults. Overall results showed that saffron possessed better efficacy in the improvement of depressive symptoms when compared with placebo, whereas saffron was as effective as synthetic antidepressants.

Bright light therapy

Main article: Seasonal affective disorder

 

Bright light therapy is sometimes used to treat depression, especially in its seasonal form.

A meta-analysis of bright light therapy commissioned by the American Psychiatric Association found a significant reduction in depression symptom severity associated with bright light treatment. Benefit was found for both seasonal affective disorder and for nonseasonal depression, with effect sizes similar to those for conventional antidepressants. For non-seasonal depression, adding light therapy to the standard antidepressant treatment was not effective. A meta-analysis of light therapy for non-seasonal depression conducted by Cochrane Collaboration, studied a different set of trials, where light was used mostly in combination with antidepressants or wake therapy. A moderate statistically significant effect of light therapy was found, with response significantly better than control treatment in high-quality studies, in studies that applied morning light treatment, and with patients who respond to total or partial sleep deprivation. Both analyses noted poor quality of most studies and their small size, and urged caution in the interpretation of their results. The short 1–2 weeks duration of most trials makes it unclear whether the effect of light therapy could be sustained in the longer term.

Exercise

Physical exercise is one recommended way to manage mild depression, such as by playing soccer.

The 2013 Cochrane Collaboration review on physical exercise for depression noted that, based upon limited evidence, it is moderately more effective than a control intervention and comparable to psychological or antidepressant drug therapies. Smaller effects were seen in more methodologically rigorous studies. Three subsequent 2014 systematic reviews that included the Cochrane review in their analysis concluded with similar findings: one indicated that physical exercise is effective as an adjunct treatment with antidepressant medication; the other two indicated that physical exercise has marked antidepressant effects and recommended the inclusion of physical activity as an adjunct treatment for mild–moderate depression and mental illness in general. These studies also found smaller effect sizes in more methodologically rigorous studies. All four systematic reviews called for more research in order to determine the efficacy or optimal exercise intensity, duration, and modality. The evidence for brain-derived neurotrophic factor (BDNF) in mediating some of the neurobiological effects of physical exercise was noted in one review which hypothesized that increased BDNF signaling is responsible for the antidepressant effect. A meta-analysis of 15 studies published in 2022 suggested a curvilinear dose-response relationship between exercise and depression risk, with low levels of exercise showing the best dose-response.

Meditation

People meditating in Madison Square Park in New York City

Mindfulness meditation programs may help improve symptoms of depression, but they are no better than active treatments such as medication, exercise, and other behavioral therapies.

Music therapy

A 2009 review found that 3 to 10 sessions of music therapy (when added to standard care) resulted in a noticeable improvement in depressive symptoms, with still greater improvement after 16 to 51 sessions.

A 2017 cochrane systematic review found that music therapy added to the usual treatment of depression gives better outcome than the usual treatment alone: "The effect size translates to a difference of 9.8 points on the HAM-D". It also found that there is no significant difference between active and receptive music therapy comparing depression outcome. It is also important to note that music therapy is not associated with more or fewer adverse events than treatment as usual.

Sleep

Depression is sometimes associated with insomnia - (difficulty in falling asleep, early waking, or waking in the middle of the night). The combination of these two results, depression and insomnia, will only worsen the situation. Hence, good sleep hygiene is important to help break this vicious circle. It would include measures such as regular sleep routines, avoidance of stimulants such as caffeine and management of sleeping disorders such as sleep apnea.

Smoking cessation

Quitting smoking cigarettes is associated with reduced depression and anxiety, with the effect "equal or larger than" those of antidepressant treatments.

Total/partial sleep deprivation

Main article: Wake therapy

Sleep deprivation (skipping a night's sleep) has been found to improve symptoms of depression in 40% - 60% of patients. Partial sleep deprivation in the second half of the night may be as effective as an all night sleep deprivation session. Improvement may last for weeks, though the majority (50%-80%) relapse after recovery sleep. Shifting or reduction of sleep time, light therapy, antidepressant drugs, and lithium have been found to potentially stabilize sleep deprivation treatment effects.

Shared Care

Shared care, when primary and specialty physicians have joint management of an individual's health care, has been shown to alleviate depression outcomes.

Research

Trials are investigating whether botulinum toxin, when used to make a person appear to frown less, stops negative feedback from the face and affects depression.

Psilocybin may have a beneficial role in the treatment of depression.

A 2019 meta-analysis found that hypnotherapy may be an effective way of alleviating the symptoms of depression.

No model of depression in animals that fully explains the mechanism of depression has been found as of 2019.

Physics of magnetic resonance imaging

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Physics_of_magnetic_resonance_imaging

 

Modern 3 tesla clinical MRI scanner.

The physics of magnetic resonance imaging (MRI) concerns fundamental physical considerations of MRI techniques and technological aspects of MRI devices. MRI is a medical imaging technique mostly used in radiology and nuclear medicine in order to investigate the anatomy and physiology of the body, and to detect pathologies including tumors, inflammation, neurological conditions such as stroke, disorders of muscles and joints, and abnormalities in the heart and blood vessels among others. Contrast agents may be injected intravenously or into a joint to enhance the image and facilitate diagnosis. Unlike CT and X-ray, MRI uses no ionizing radiation and is, therefore, a safe procedure suitable for diagnosis in children and repeated runs. Patients with specific non-ferromagnetic metal implants, cochlear implants, and cardiac pacemakers nowadays may also have an MRI in spite of effects of the strong magnetic fields. This does not apply on older devices, and details for medical professionals are provided by the device's manufacturer.

Certain atomic nuclei are able to absorb and emit radio frequency energy when placed in an external magnetic field. In clinical and research MRI, hydrogen atoms are most often used to generate a detectable radio-frequency signal that is received by antennas in close proximity to the anatomy being examined. Hydrogen atoms are naturally abundant in people and other biological organisms, particularly in water and fat. For this reason, most MRI scans essentially map the location of water and fat in the body. Pulses of radio waves excite the nuclear spin energy transition, and magnetic field gradients localize the signal in space. By varying the parameters of the pulse sequence, different contrasts may be generated between tissues based on the relaxation properties of the hydrogen atoms therein.

When inside the magnetic field (B₀) of the scanner, the magnetic moments of the protons align to be either parallel or anti-parallel to the direction of the field. While each individual proton can only have one of two alignments, the collection of protons appear to behave as though they can have any alignment. Most protons align parallel to B₀ as this is a lower energy state. A radio frequency pulse is then applied, which can excite protons from parallel to anti-parallel alignment, only the latter are relevant to the rest of the discussion. In response to the force bringing them back to their equilibrium orientation, the protons undergo a rotating motion (precession), much like a spun wheel under the effect of gravity. The protons will return to the low energy state by the process of spin-lattice relaxation. This appears as a magnetic flux, which yields a changing voltage in receiver coils to give the signal. The frequency at which a proton or group of protons in a voxel resonates depends on the strength of the local magnetic field around the proton or group of protons, a stronger field corresponds to a larger energy difference and higher frequency photons. By applying additional magnetic fields (gradients) that vary linearly over space, specific slices to be imaged can be selected, and an image is obtained by taking the 2-D Fourier transform of the spatial frequencies of the signal (k-space). Due to the magnetic Lorentz force from B₀ on the current flowing in the gradient coils, the gradient coils will try to move producing loud knocking sounds, for which patients require hearing protection.

History

The MRI scanner was developed from 1975 to 1977 at the University of Nottingham by Prof Raymond Andrew FRS FRSE following from his research into nuclear magnetic resonance. The full body scanner was created in 1978.

Nuclear magnetism

Main article: Nuclear magnetic resonance

Subatomic particles have the quantum mechanical property of spin. Certain nuclei such as ¹H (protons), ²H, ³He, ²³Na or ³¹P, have a non–zero spin and therefore a magnetic moment. In the case of the so-called spin-1⁄2 nuclei, such as ¹H, there are two spin states, sometimes referred to as up and down. Nuclei such as ¹²C have no unpaired neutrons or protons, and no net spin; however, the isotope ¹³C does.

When these spins are placed in a strong external magnetic field they precess around an axis along the direction of the field. Protons align in two energy eigenstates (the Zeeman effect): one low-energy and one high-energy, which are separated by a very small splitting energy.

Resonance and relaxation

Main article: Relaxation (NMR)

Quantum mechanics is required to accurately model the behaviour of a single proton. However, classical mechanics can be used to describe the behaviour of an ensemble of protons adequately. As with other spin ${\displaystyle 1/2}$ particles, whenever the spin of a single proton is measured it can only have one of two results commonly called parallel and anti-parallel. When we discuss the state of a proton or protons we are referring to the wave function of that proton which is a linear combination of the parallel and anti-parallel states.

In the presence of the magnetic field, B₀, the protons will appear to precess at the Larmor frequency determined by the particle's gyro-magnetic ratio and the strength of the field. The static fields used most commonly in MRI cause precession which corresponds to a radiofrequency (RF) photon.

The net longitudinal magnetization in thermodynamic equilibrium is due to a tiny excess of protons in the lower energy state. This gives a net polarization that is parallel to the external field. Application of an RF pulse can tip this net polarization vector sideways (with, i.e., a so-called 90° pulse), or even reverse it (with a so-called 180° pulse). The protons will come into phase with the RF pulse and therefore each other.

The recovery of longitudinal magnetization is called longitudinal or T₁ relaxation and occurs exponentially with a time constant T₁. The loss of phase coherence in the transverse plane is called transverse or T₂ relaxation. T₁ is thus associated with the enthalpy of the spin system, or the number of nuclei with parallel versus anti-parallel spin. T₂ on the other hand is associated with the entropy of the system, or the number of nuclei in phase.

When the radio frequency pulse is turned off, the transverse vector component produces an oscillating magnetic field which induces a small current in the receiver coil. This signal is called the free induction decay (FID). In an idealized nuclear magnetic resonance experiment, the FID decays approximately exponentially with a time constant T₂. However, in practical MRI there are small differences in the static magnetic field at different spatial locations ("inhomogeneities") that cause the Larmor frequency to vary across the body. This creates destructive interference, which shortens the FID. The time constant for the observed decay of the FID is called the T^*
₂ relaxation time, and is always shorter than T₂. At the same time, the longitudinal magnetization starts to recover exponentially with a time constant T₁ which is much larger than T₂ (see below).

In MRI, the static magnetic field is augmented by a field gradient coil to vary across the scanned region, so that different spatial locations become associated with different precession frequencies. Only those regions where the field is such that the precession frequencies match the RF frequency will experience excitation. Usually, these field gradients are modulated to sweep across the region to be scanned, and it is the almost infinite variety of RF and gradient pulse sequences that gives MRI its versatility. Change of field gradient spreads the responding FID signal in the frequency domain, but this can be recovered and measured by a refocusing gradient (to create a so-called "gradient echo"), or by a radio frequency pulse (to create a so-called "spin-echo"), or in digital post-processing of the spread signal. The whole process can be repeated when some T₁-relaxation has occurred and the thermal equilibrium of the spins has been more or less restored. The repetition time (TR) is the time between two successive excitations of the same slice.

Typically, in soft tissues T₁ is around one second while T₂ and T^*
₂ are a few tens of milliseconds. However, these values can vary widely between different tissues, as well as between different external magnetic fields. This behavior is one factor giving MRI its tremendous soft tissue contrast.

MRI contrast agents, such as those containing Gadolinium(III) work by altering (shortening) the relaxation parameters, especially T₁.

Imaging

Imaging schemes

A number of schemes have been devised for combining field gradients and radio frequency excitation to create an image:

• 2D or 3D reconstruction from projections, such as in computed tomography.
• Building the image point-by-point or line-by-line.
• Gradients in the RF field rather than the static field.

Although each of these schemes is occasionally used in specialist applications, the majority of MR Images today are created either by the two-dimensional Fourier transform (2DFT) technique with slice selection, or by the three-dimensional Fourier transform (3DFT) technique. Another name for 2DFT is spin-warp. What follows here is a description of the 2DFT technique with slice selection.

The 3DFT technique is rather similar except that there is no slice selection and phase-encoding is performed in two separate directions.

Echo-planar imaging

Another scheme which is sometimes used, especially in brain scanning or where images are needed very rapidly, is called echo-planar imaging (EPI): In this case, each RF excitation is followed by a train of gradient echoes with different spatial encoding. Multiplexed-EPI is even faster, e.g., for whole brain functional MRI (fMRI) or diffusion MRI.

Image contrast and contrast enhancement

Image contrast is created by differences in the strength of the NMR signal recovered from different locations within the sample. This depends upon the relative density of excited nuclei (usually water protons), on differences in relaxation times (T₁, T₂, and T^*
₂) of those nuclei after the pulse sequence, and often on other parameters discussed under specialized MR scans. Contrast in most MR images is actually a mixture of all these effects, but careful design of the imaging pulse sequence allows one contrast mechanism to be emphasized while the others are minimized. The ability to choose different contrast mechanisms gives MRI tremendous flexibility. In the brain, T₁-weighting causes the nerve connections of white matter to appear white, and the congregations of neurons of gray matter to appear gray, while cerebrospinal fluid (CSF) appears dark. The contrast of white matter, gray matter and cerebrospinal fluid is reversed using T₂ or T^*
₂ imaging, whereas proton-density-weighted imaging provides little contrast in healthy subjects. Additionally, functional parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV) or blood oxygenation can affect T₁, T₂, and T^*
₂ and so can be encoded with suitable pulse sequences.

In some situations it is not possible to generate enough image contrast to adequately show the anatomy or pathology of interest by adjusting the imaging parameters alone, in which case a contrast agent may be administered. This can be as simple as water, taken orally, for imaging the stomach and small bowel. However, most contrast agents used in MRI are selected for their specific magnetic properties. Most commonly, a paramagnetic contrast agent (usually a gadolinium compound) is given. Gadolinium-enhanced tissues and fluids appear extremely bright on T₁-weighted images. This provides high sensitivity for detection of vascular tissues (e.g., tumors) and permits assessment of brain perfusion (e.g., in stroke). There have been concerns raised recently regarding the toxicity of gadolinium-based contrast agents and their impact on persons with impaired kidney function. (See Safety/Contrast agents below.)

More recently, superparamagnetic contrast agents, e.g., iron oxide nanoparticles, have become available. These agents appear very dark on T^*
₂-weighted images and may be used for liver imaging, as normal liver tissue retains the agent, but abnormal areas (e.g., scars, tumors) do not. They can also be taken orally, to improve visualization of the gastrointestinal tract, and to prevent water in the gastrointestinal tract from obscuring other organs (e.g., the pancreas). Diamagnetic agents such as barium sulfate have also been studied for potential use in the gastrointestinal tract, but are less frequently used.

k-space

Main article: K-space (MRI)

In 1983, Ljunggren and Twieg independently introduced the k-space formalism, a technique that proved invaluable in unifying different MR imaging techniques. They showed that the demodulated MR signal S(t) generated by the interaction between an ensemble of freely precessing nuclear spins in the presence of a linear magnetic field gradient G and a receiver-coil equals the Fourier transform of the effective spin density, ${\displaystyle \rho (\overrightarrow{x})}$. Fundamentally, the signal is derived from Faraday's law of induction:

${\displaystyle S(t)={\tilde{\rho }}_{\mathrm{e}\mathrm{f}\mathrm{f}}\left(\overrightarrow{k}(t)\right)\equiv {\int }_{-\mathrm{\infty }}^{\mathrm{\infty }}\mathrm{d}\overrightarrow{x}\rho (\overrightarrow{x})\cdot e^{2\pi i\overrightarrow{k}(t)\cdot \overrightarrow{x}}}$

where:

${\displaystyle \overrightarrow{k}(t)\equiv {\int }_0^t\overrightarrow{G}(\tau )\mathrm{d}\tau }$

In other words, as time progresses the signal traces out a trajectory in k-space with the velocity vector of the trajectory proportional to the vector of the applied magnetic field gradient. By the term effective spin density we mean the true spin density ${\displaystyle \rho (\overrightarrow{x})}$ corrected for the effects of T₁ preparation, T₂ decay, dephasing due to field inhomogeneity, flow, diffusion, etc. and any other phenomena that affect that amount of transverse magnetization available to induce signal in the RF probe or its phase with respect to the receiving coil' s electromagnetic field.

From the basic k-space formula, it follows immediately that we reconstruct an image ${\displaystyle I(\overrightarrow{x})}$ by taking the inverse Fourier transform of the sampled data, viz.

${\displaystyle I\left(\overrightarrow{x}\right)={\int }_{-\mathrm{\infty }}^{\mathrm{\infty }}\mathrm{d}\overrightarrow{k}S\left(\overrightarrow{k}(t)\right)\cdot e^{-2\pi i\overrightarrow{k}(t)\cdot \overrightarrow{x}}}$

Using the k-space formalism, a number of seemingly complex ideas became simple. For example, it becomes very easy (for physicists, in particular) to understand the role of phase encoding (the so-called spin-warp method). In a standard spin echo or gradient echo scan, where the readout (or view) gradient is constant (e.g., G), a single line of k-space is scanned per RF excitation. When the phase encoding gradient is zero, the line scanned is the k_x axis. When a non-zero phase-encoding pulse is added in between the RF excitation and the commencement of the readout gradient, this line moves up or down in k-space, i.e., we scan the line k_y = constant.

The k-space formalism also makes it very easy to compare different scanning techniques. In single-shot EPI, all of k-space is scanned in a single shot, following either a sinusoidal or zig-zag trajectory. Since alternating lines of k-space are scanned in opposite directions, this must be taken into account in the reconstruction. Multi-shot EPI and fast spin echo techniques acquire only part of k-space per excitation. In each shot, a different interleaved segment is acquired, and the shots are repeated until k-space is sufficiently well-covered. Since the data at the center of k-space represent lower spatial frequencies than the data at the edges of k-space, the T_E value for the center of k-space determines the image's T₂ contrast.

The importance of the center of k-space in determining image contrast can be exploited in more advanced imaging techniques. One such technique is spiral acquisition—a rotating magnetic field gradient is applied, causing the trajectory in k-space to spiral out from the center to the edge. Due to T₂ and T^*
₂ decay the signal is greatest at the start of the acquisition, hence acquiring the center of k-space first improves contrast to noise ratio (CNR) when compared to conventional zig-zag acquisitions, especially in the presence of rapid movement.

Since ${\displaystyle \overrightarrow{x}}$ and ${\displaystyle \overrightarrow{k}}$ are conjugate variables (with respect to the Fourier transform) we can use the Nyquist theorem to show that a step in k-space determines the field of view of the image (maximum frequency that is correctly sampled) and the maximum value of k sampled determines the resolution; i.e.,

${\displaystyle \mathrm{F}\mathrm{O}\mathrm{V}\propto \frac{1}{\mathrm{\Delta }k}\mathrm{R}\mathrm{e}\mathrm{s}\mathrm{o}\mathrm{l}\mathrm{u}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}\propto |k_{max}|.}$

(These relationships apply to each axis independently.)

Example of a pulse sequence

Simplified timing diagram for two-dimensional-Fourier-transform (2DFT) Spin Echo (SE) pulse sequence

In the timing diagram, the horizontal axis represents time. The vertical axis represents: (top row) amplitude of radio frequency pulses; (middle rows) amplitudes of the three orthogonal magnetic field gradient pulses; and (bottom row) receiver analog-to-digital converter (ADC). Radio frequencies are transmitted at the Larmor frequency of the nuclide to be imaged. For example, for ¹H in a magnetic field of 1 T, a frequency of 42.5781 MHz would be employed. The three field gradients are labeled G_X (typically corresponding to a patient's left-to-right direction and colored red in diagram), G_Y (typically corresponding to a patient's front-to-back direction and colored green in diagram), and G_Z (typically corresponding to a patient's head-to-toe direction and colored blue in diagram). Where negative-going gradient pulses are shown, they represent reversal of the gradient direction, i.e., right-to-left, back-to-front or toe-to-head. For human scanning, gradient strengths of 1–100 mT/m are employed: Higher gradient strengths permit better resolution and faster imaging. The pulse sequence shown here would produce a transverse (axial) image.

The first part of the pulse sequence, SS, achieves "slice selection". A shaped pulse (shown here with a sinc modulation) causes a 90° nutation of longitudinal nuclear magnetization within a slab, or slice, creating transverse magnetization. The second part of the pulse sequence, PE, imparts a phase shift upon the slice-selected nuclear magnetization, varying with its location in the Y direction. The third part of the pulse sequence, another slice selection (of the same slice) uses another shaped pulse to cause a 180° rotation of transverse nuclear magnetization within the slice. This transverse magnetisation refocuses to form a spin echo at a time T_E. During the spin echo, a frequency-encoding (FE) or readout gradient is applied, making the resonant frequency of the nuclear magnetization vary with its location in the X direction. The signal is sampled n_FE times by the ADC during this period, as represented by the vertical lines. Typically n_FE of between 128 and 512 samples are taken.

The longitudinal magnetisation is then allowed to recover somewhat and after a time T_R the whole sequence is repeated n_PE times, but with the phase-encoding gradient incremented (indicated by the horizontal hatching in the green gradient block). Typically n_PE of between 128 and 512 repetitions are made.

The negative-going lobes in G_X and G_Z are imposed to ensure that, at time T_E (the spin echo maximum), phase only encodes spatial location in the Y direction.

Typically T_E is between 5 ms and 100 ms, while T_R is between 100 ms and 2000 ms.

After the two-dimensional matrix (typical dimension between 128 × 128 and 512 × 512) has been acquired, producing the so-called k-space data, a two-dimensional inverse Fourier transform is performed to provide the familiar MR image. Either the magnitude or phase of the Fourier transform can be taken, the former being far more common.

Overview of main sequences

Main article: MRI sequence

Group	Sequence	Abbr.	Physics	Main clinical distinctions	Example
Spin echo	T1 weighted	T1	Measuring spin–lattice relaxation by using a short repetition time (TR) and echo time (TE).	Lower signal for more water content, as in edema, tumor, infarction, inflammation, infection, hyperacute or chronic hemorrhage. High signal for fat High signal for paramagnetic substances, such as MRI contrast agents Standard foundation and comparison for other sequences
	T2 weighted	T2	Measuring spin–spin relaxation by using long TR and TE times	Higher signal for more water content Low signal for fat − Note that this only applies to standard Spin Echo (SE) sequences and not the more modern Fast Spin Echo (FSE) sequence (also referred to as Turbo Spin Echo, TSE), which is the most commonly used technique today. In FSE/TSE, fat will have a high signal. Low signal for paramagnetic substances Standard foundation and comparison for other sequences
	Proton density weighted	PD	Long TR (to reduce T1) and short TE (to minimize T2).	Joint disease and injury. High signal from meniscus tears. (pictured)
Gradient echo (GRE)	Steady-state free precession	SSFP	Maintenance of a steady, residual transverse magnetisation over successive cycles.	Creation of cardiac MRI videos (pictured).
	Effective T2 or "T2-star"	T2*	Spoiled gradient recalled echo (GRE) with a long echo time and small flip angle	Low signal from hemosiderin deposits (pictured) and hemorrhages.
	Susceptibility-weighted	SWI	Spoiled gradient recalled echo (GRE), fully flow compensated, long echo time, combines phase image with magnitude image	Detecting small amounts of hemorrhage (diffuse axonal injury pictured) or calcium.
Inversion recovery	Short tau inversion recovery	STIR	Fat suppression by setting an inversion time where the signal of fat is zero.	High signal in edema, such as in more severe stress fracture. Shin splints pictured:
	Fluid-attenuated inversion recovery	FLAIR	Fluid suppression by setting an inversion time that nulls fluids	High signal in lacunar infarction, multiple sclerosis (MS) plaques, subarachnoid haemorrhage and meningitis (pictured).
	Double inversion recovery	DIR	Simultaneous suppression of cerebrospinal fluid and white matter by two inversion times.	High signal of multiple sclerosis plaques (pictured).
Diffusion weighted (DWI)	Conventional	DWI	Measure of Brownian motion of water molecules.	High signal within minutes of cerebral infarction (pictured).
	Apparent diffusion coefficient	ADC	Reduced T2 weighting by taking multiple conventional DWI images with different DWI weighting, and the change corresponds to diffusion.	Low signal minutes after cerebral infarction (pictured).
	Diffusion tensor	DTI	Mainly tractography (pictured) by an overall greater Brownian motion of water molecules in the directions of nerve fibers.	Evaluating white matter deformation by tumors Reduced fractional anisotropy may indicate dementia.
Perfusion weighted (PWI)	Dynamic susceptibility contrast	DSC	Measures changes over time in susceptibility-induced signal loss due to gadolinium contrast injection.	Provides measurements of blood flow In cerebral infarction, the infarcted core and the penumbra have decreased perfusion and delayed contrast arrival (pictured).
	Arterial spin labelling	ASL	Magnetic labeling of arterial blood below the imaging slab, which subsequently enters the region of interest. It does not need gadolinium contrast.
	Dynamic contrast enhanced	DCE	Measures changes over time in the shortening of the spin–lattice relaxation (T1) induced by a gadolinium contrast bolus.	Faster Gd contrast uptake along with other features is suggestive of malignancy (pictured).
Functional MRI (fMRI)	Blood-oxygen-level dependent imaging	BOLD	Changes in oxygen saturation-dependent magnetism of hemoglobin reflects tissue activity.	Localizing brain activity from performing an assigned task (e.g. talking, moving fingers) before surgery, also used in research of cognition.
Magnetic resonance angiography (MRA) and venography	Time-of-flight	TOF	Blood entering the imaged area is not yet magnetically saturated, giving it a much higher signal when using short echo time and flow compensation.	Detection of aneurysm, stenosis, or dissection
	Phase-contrast magnetic resonance imaging	PC-MRA	Two gradients with equal magnitude, but opposite direction, are used to encode a phase shift, which is proportional to the velocity of spins.	Detection of aneurysm, stenosis, or dissection (pictured).	(VIPR)

MRI scanner

Construction and operation

Schematic of construction of a cylindrical superconducting MR scanner

The major components of an MRI scanner are: the main magnet, which polarizes the sample, the shim coils for correcting inhomogeneities in the main magnetic field, the gradient system which is used to localize the MR signal and the RF system, which excites the sample and detects the resulting NMR signal. The whole system is controlled by one or more computers.

Magnet

A mobile MRI unit visiting Glebefields Health Centre, Tipton, England

The magnet is the largest and most expensive component of the scanner, and the remainder of the scanner is built around it. The strength of the magnet is measured in teslas (T). Clinical magnets generally have a field strength in the range 0.1–3.0 T, with research systems available up to 9.4 T for human use and 21 T for animal systems. In the United States, field strengths up to 4 T have been approved by the FDA for clinical use.

Just as important as the strength of the main magnet is its precision. The straightness of the magnetic lines within the center (or, as it is technically known, the iso-center) of the magnet needs to be near-perfect. This is known as homogeneity. Fluctuations (inhomogeneities in the field strength) within the scan region should be less than three parts per million (3 ppm). Three types of magnets have been used:

• Permanent magnet: Conventional magnets made from ferromagnetic materials (e.g., steel alloys containing rare-earth elements such as neodymium) can be used to provide the static magnetic field. A permanent magnet that is powerful enough to be used in an MRI will be extremely large and bulky; they can weigh over 100 tonnes. Permanent magnet MRIs are very inexpensive to maintain; this cannot be said of the other types of MRI magnets, but there are significant drawbacks to using permanent magnets. They are only capable of achieving weak field strengths compared to other MRI magnets (usually less than 0.4 T) and they are of limited precision and stability. Permanent magnets also present special safety issues; since their magnetic fields cannot be "turned off," ferromagnetic objects are virtually impossible to remove from them once they come into direct contact. Permanent magnets also require special care when they are being brought to their site of installation.
• Resistive electromagnet: A solenoid wound from copper wire is an alternative to a permanent magnet. An advantage is low initial cost, but field strength and stability are limited. The electromagnet requires considerable electrical energy during operation which can make it expensive to operate. This design is essentially obsolete.
• Superconducting electromagnet: When a niobium-titanium or niobium-tin alloy is cooled by liquid helium to 4 K (−269 °C, −452 °F) it becomes a superconductor, losing resistance to flow of electric current. An electromagnet constructed with superconductors can have extremely high field strengths, with very high stability. The construction of such magnets is extremely costly, and the cryogenic helium is expensive and difficult to handle. However, despite their cost, helium cooled superconducting magnets are the most common type found in MRI scanners today.

Most superconducting magnets have their coils of superconductive wire immersed in liquid helium, inside a vessel called a cryostat. Despite thermal insulation, sometimes including a second cryostat containing liquid nitrogen, ambient heat causes the helium to slowly boil off. Such magnets, therefore, require regular topping-up with liquid helium. Generally a cryocooler, also known as a coldhead, is used to recondense some helium vapor back into the liquid helium bath. Several manufacturers now offer 'cryogenless' scanners, where instead of being immersed in liquid helium the magnet wire is cooled directly by a cryocooler. Alternatively, the magnet may be cooled by carefully placing liquid helium in strategic spots, dramatically reducing the amount of liquid helium used, or, high temperature superconductors may be used instead.

Magnets are available in a variety of shapes. However, permanent magnets are most frequently 'C' shaped, and superconducting magnets most frequently cylindrical. C-shaped superconducting magnets and box-shaped permanent magnets have also been used.

Magnetic field strength is an important factor in determining image quality. Higher magnetic fields increase signal-to-noise ratio, permitting higher resolution or faster scanning. However, higher field strengths require more costly magnets with higher maintenance costs, and have increased safety concerns. A field strength of 1.0–1.5 T is a good compromise between cost and performance for general medical use. However, for certain specialist uses (e.g., brain imaging) higher field strengths are desirable, with some hospitals now using 3.0 T scanners.

FID signal from a badly shimmed sample has a complex envelope.

 

FID signal from a well shimmed sample, showing a pure exponential decay.

Shims

When the MR scanner is placed in the hospital or clinic, its main magnetic field is far from being homogeneous enough to be used for scanning. That is why before doing fine tuning of the field using a sample, the magnetic field of the magnet must be measured and shimmed.

After a sample is placed into the scanner, the main magnetic field is distorted by susceptibility boundaries within that sample, causing signal dropout (regions showing no signal) and spatial distortions in acquired images. For humans or animals the effect is particularly pronounced at air-tissue boundaries such as the sinuses (due to paramagnetic oxygen in air) making, for example, the frontal lobes of the brain difficult to image. To restore field homogeneity a set of shim coils is included in the scanner. These are resistive coils, usually at room temperature, capable of producing field corrections distributed as several orders of spherical harmonics.

After placing the sample in the scanner, the B₀ field is 'shimmed' by adjusting currents in the shim coils. Field homogeneity is measured by examining an FID signal in the absence of field gradients. The FID from a poorly shimmed sample will show a complex decay envelope, often with many humps. Shim currents are then adjusted to produce a large amplitude exponentially decaying FID, indicating a homogeneous B₀ field. The process is usually automated.

Gradients

Gradient coils are used to spatially encode the positions of protons by varying the magnetic field linearly across the imaging volume. The Larmor frequency will then vary as a function of position in the x, y and z-axes.

Gradient coils are usually resistive electromagnets powered by sophisticated amplifiers which permit rapid and precise adjustments to their field strength and direction. Typical gradient systems are capable of producing gradients from 20 to 100 mT/m (i.e., in a 1.5 T magnet, when a maximal z-axis gradient is applied, the field strength may be 1.45 T at one end of a 1 m long bore and 1.55 T at the other). It is the magnetic gradients that determine the plane of imaging—because the orthogonal gradients can be combined freely, any plane can be selected for imaging.

Scan speed is dependent on performance of the gradient system. Stronger gradients allow for faster imaging, or for higher resolution; similarly, gradient systems capable of faster switching can also permit faster scanning. However, gradient performance is limited by safety concerns over nerve stimulation.

Some important characteristics of gradient amplifiers and gradient coils are slew rate and gradient strength. As mentioned earlier, a gradient coil will create an additional, linearly varying magnetic field that adds or subtracts from the main magnetic field. This additional magnetic field will have components in all 3 directions, viz. x, y and z; however, only the component along the magnetic field (usually called the z-axis, hence denoted G_z) is useful for imaging. Along any given axis, the gradient will add to the magnetic field on one side of the zero position and subtract from it on the other side. Since the additional field is a gradient, it has units of gauss per centimeter or millitesla per meter (mT/m). High performance gradient coils used in MRI are typically capable of producing a gradient magnetic field of approximate 30 mT/m or higher for a 1.5 T MRI. The slew rate of a gradient system is a measure of how quickly the gradients can be ramped on or off. Typical higher performance gradients have a slew rate of up to 100–200 T·m⁻¹·s⁻¹. The slew rate depends both on the gradient coil (it takes more time to ramp up or down a large coil than a small coil) and on the performance of the gradient amplifier (it takes a lot of voltage to overcome the inductance of the coil) and has significant influence on image quality.

Radio frequency system

The radio frequency (RF) transmission system consists of an RF synthesizer, power amplifier and transmitting coil. That coil is usually built into the body of the scanner. The power of the transmitter is variable, but high-end whole-body scanners may have a peak output power of up to 35 kW, and be capable of sustaining average power of 1 kW. Although these electromagnetic fields are in the RF range of tens of megahertz (often in the shortwave radio portion of the electromagnetic spectrum) at powers usually exceeding the highest powers used by amateur radio, there is very little RF interference produced by the MRI machine. The reason for this, is that the MRI is not a radio transmitter. The RF frequency electromagnetic field produced in the "transmitting coil" is a magnetic near-field with very little associated changing electric field component (such as all conventional radio wave transmissions have). Thus, the high-powered electromagnetic field produced in the MRI transmitter coil does not produce much electromagnetic radiation at its RF frequency, and the power is confined to the coil space and not radiated as "radio waves." Thus, the transmitting coil is a good EM field transmitter at radio frequency, but a poor EM radiation transmitter at radio frequency.

The receiver consists of the coil, pre-amplifier and signal processing system. The RF electromagnetic radiation produced by nuclear relaxation inside the subject is true EM radiation (radio waves), and these leave the subject as RF radiation, but they are of such low power as to also not cause appreciable RF interference that can be picked up by nearby radio tuners (in addition, MRI scanners are generally situated in metal mesh lined rooms which act as Faraday cages.)

While it is possible to scan using the integrated coil for RF transmission and MR signal reception, if a small region is being imaged, then better image quality (i.e., higher signal-to-noise ratio) is obtained by using a close-fitting smaller coil. A variety of coils are available which fit closely around parts of the body such as the head, knee, wrist, breast, or internally, e.g., the rectum.

A recent development in MRI technology has been the development of sophisticated multi-element phased array coils which are capable of acquiring multiple channels of data in parallel. This 'parallel imaging' technique uses unique acquisition schemes that allow for accelerated imaging, by replacing some of the spatial coding originating from the magnetic gradients with the spatial sensitivity of the different coil elements. However, the increased acceleration also reduces the signal-to-noise ratio and can create residual artifacts in the image reconstruction. Two frequently used parallel acquisition and reconstruction schemes are known as SENSE and GRAPPA. A detailed review of parallel imaging techniques can be found here: