Brain SPECT Imaging: Uses and Benefits in Clinical Psychiatric Practice

By Daniel G. Amen, MD and Theodore Henderson, MD, PhD

Is it bipolar disorder or brain trauma? Depression or toxic exposure? Is my depressed patient’s brain overactive and needs a treatment to calm it down, or is it underactive and needs to be stimulated?  How would you ever know unless you actually looked?

Using brain SPECT imaging in clinical psychiatric practice is evidence-based. According to the AmericanCollege of Radiology1 and the European Association of Nuclear Medicine (EANM)2, brain SPECT imaging is indicated for evaluation of cerebral vascular disease, epilepsy, dementia, brain trauma, encephalitis, and movement disorders (common issues for psychiatrists). If psychiatrists only ordered SPECT for commonly accepted indications they would be ordering hundreds of thousands of scans each year. For example, depression, anxiety, personality changes, and attentional issues are common sequalae of brain injury3-6. Moreover, the EANM guidelines state, “SPECT can be useful in other indications such as psychiatric diseases (e.g. for follow-up of depression).

Yet, psychiatry remains the only medical specialty that rarely looks at the organ it treats. Cardiologists look … neurologists look… gastroenterologists look. All other medical specialists evaluate the organs they treat. Psychiatrists guess, which is holding our field back.

While the DSM-IV is the current gold standard for psychiatric diagnosis, its limitations are perhaps made most evident by the fact that treatment effectiveness rates, have shown little improvement from what they were in the 1970s, despite 40 years of randomized controlled trials (RCT) resulting in more than 130 FDA approved medications used in treating various DSM defined disorders. DePaulo7 summarized the results of the largest “effectiveness plus” studies ever conducted for bipolar disorder (STEP-BD), major depression (STAR*D), and antipsychotics (CATIE), “the three studies taken together, however, underline the suggestion that modern pharmacological treatments may be no more beneficial than older ones, despite their added cost.” Insel made similar observations, “The unfortunate reality is that current medications help too few people to get better and very few people to get well.” 8

We argue that the failure of these medications is not only due to their incomplete mechanisms of action, but also due to the poor identification of the underlying neurobiological mechanisms which they are intended to target. Identifying additional procedures to properly diagnose patients, and thereby better tailor their treatment, is critical to advancing psychiatric practice.

SPECT, used in combination with detailed clinical histories and mental status examinations, which is the method we have used for many years and thousands of patients, increases diagnostic certainty, reduces the number of medication trials, identifies unrecognized brain injury (whether traumatic or toxic), and improves patient compliance.

There is a rich basis in the medical literature for understanding the neurological processes underlying many psychiatric disorders. For example, patients with ADHD has been consistently demonstrated to have decreased perfusion in the orbital frontal cortex, lateral prefrontal cortex, and temporal lobes9-13. These findings are in contrast to those of bipolar disorder14, which can present with strongly overlapping symptoms making clinical differentiation challenging. Likewise, depression and dementia can present with overlapping symptoms in the elderly. However, functional neuroimaging can differentiate these disorders. Studies of Alzheimer’s using perfusion SPECT followed over a longitudinal clinical course and/or histopathology demonstrate a sensitivity in the range of 82-96% and a specificity in the range of 84-89%15-16 and can be clearly distinguished from depression17,18. Deep brain stimulation can be effective in treatment-resistant depression, but this surgical intervention is not attempted without confirming the underlying neurological process of overactive subgenual anterior cingulate gyrus19.

In a recent study20, seven board certified psychiatrists evaluated 109 patient files that included clinical histories and mental status exams, without the SPECT images, and gave diagnoses and treatment recommendations. They were then given the SPECT data. The scans changed the initial diagnoses or treatment recommendations in 79% of cases. Twenty-two percent showed an unexpected brain trauma, 22% had unexpected toxicity, and 60% showed new targets for medications.

These findings are consistent with Borghesani et al.21 who found that SPECT confirmed, clarified, or contradicted initial clinical diagnosis in greater than 80% of patients with possible dementia. “Neuroimaging was useful even if it only confirmed the diagnosis … Seeing the disease process increased diagnostic confidence and clinician’s ability to explain symptoms to patients and families … Images have a special resonance for patients/families, grounding symptoms in observable brain changes.”

How does SPECT change psychiatric diagnosis and treatment?  What can SPECT scan tell clinicians and patients that they cannot obtain through history, mental status examinations, physical examinations or neuropsychological testing?

1. SPECT teaches you to ask better questions. Dr. Harold Bursztajn from Harvard says, “SPECT doesn’t give you the answer, it teaches you to ask better questions.”  It helps to understand the underlying physiology of disorders.

2. SPECT helps to prevent mistakes, such as stimulating an overactive brain or calming a brain that is already low in activity. With SPECT, in complex or treatment resistant cases, there are often unexpected findings that may be contributing to problems, such as inflammation, trauma, or toxicity.

3. SPECT aids in the diagnosis and treatment of substance abusers. It helps to break denial (hard to be in denial when you see a “toxic” looking scan). It also increases compliance, helps to understand co-morbidity, and can be useful in drug education.

4. SPECT helps to subtype psychiatric illnesses. Giving someone the diagnosis of depression is like giving them the diagnosis of chest pain. There are too many causes, which is one of the reasons antidepressant studies have such poor outcomes. It is not that our medications are ineffective, it is that we are not tailoring the treatment to the type of brain each patient possesses. Brockman demonstrated SPECT’s usefulness in choosing between treatments for depression22.

5. SPECT increases compliance as patients can see they have a problem.

6. SPECT helps families as they begin to see problems as medical not moral. It decreases shame, guilt, stigma, and self-loathing, and increases forgiveness and compassion. We have nothing else in psychiatry that is this powerful or this immediate.

Often, a careful clinical evaluation can accurately diagnose many psychiatric disorders. SPECT’s best use is in complex or treatment-resistant cases. Withholding imaging in unclear cases does an injustice to our patients and can harm them. Multiple trials of ineffective or inappropriate medications, delays in identifying comorbid conditions, targeting the wrong neurobiological process of a psychiatric symptom (treating anxious inattention with a stimulant), and the delay in recovery are expensive and dangerous.

For example, adults labeled as “personality disordered” often on SPECT can show temporal lobe dysfunction23,24, frontal lobe trauma or dysfunction25,26, brain toxicity27,28, or findings consistent with ADHD29. Children who present with rage outbursts30 commonly show temporal lobe abnormalities31, OCD32, bipolar disorder30,33, ADHD30,33, brain trauma34 or toxicity35.

Below we’ve listed the arguments posed against SPECT in clinical practice by our colleagues at the recent APA debate and, in parentheses, our brief response.

1. SPECT is not standard of care. (What innovation is? Deep brain stimulation was considered radical at one point. Its use also is rooted in the recognized value of functional neuroimaging.)

2. There is a cost to doing scans. (We argue that it is much more expensive and potentially lethal to have an ineffectively treated psychiatric disorder or multiple failed treatment trials).

3. There is radiation with the scans. (The radiation level is about 640 mRems which is roughly1.5 times the annual background radiation for Denver, Colorado36,37. The dose is less than that of most CT scans36. Ernst and colleagues reviewed this issue extensively and concluded that radiation exposures of this level are not significantly harmful38.

4. There is not enough research. (There are numerous, and a wide range of studies demonstrating SPECT’s usefulness in a number of diagnoses.)

5. Our work with tens of thousands of patients is “anecdotal.” (We have published more than 40 peer-reviewed studies on SPECT in psychiatry.)

6. SPECT is not ready, and it should be left in the hands of researchers. (We believe this is a disturbing argument, as it aims to withhold a useful medical procedure to patients who could benefit from it now.)

At the debate we referenced a 1993 study presented at the APA by Drs. Sam Mehr and Tom Jaeger from Creighton University on 100 bipolar teenagers. Fifty were scanned on the day of admission, fifty were never scanned. The average length of stay in the “never scanned” group was 44 days. The average length of stay in the scanned group was 17 days, which was a significant cost savings, consistent with our experience.

By not using functional imaging routinely in clinical practice we hurt patients and their families, we diminish our profession, and patients are mislabeled and mistreated. We believe that soon it will be malpractice not to order functional imaging in complex cases.

 

 

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  1. Hussein M, Abdel-Dayem MD. ACR practice guideline for the performance of single-photon emission computed tomography (SPECT) brain perfusion imaging. SPECT Brain Perfusion Imaging  2006, 667-671. epub
  2. Tatsch K, Asenbaum S, Bartenstein P, Catafau A, Halldin C, Pilowsky LS, Pupi, A. European Association of Nuclear Medicine Procedure Guidelines for brain perfusion SPECT using 99mTc-labelled radiopharmaceuticals. European Journal of Nuclear Medicine, 2002 29:BP36-BP42
  3. Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. (2004). Major depression following traumatic brain injury. Arch Gen Psychiatry,2004;61(1):42-50.
  4. Fann JR, Burington B, Leonetti A, Jaffe K, Katon WJ, Thompson R.S. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry, 2004;61(1):53-61.
  5. Levin H, Hanten G, Max J, Li X, Swank P, Ewing-Cobbs L, Dennis M, Menefee DS, Schachar R. Symptoms of attention-deficit/hyperactivity disorder following traumatic brain injury in children. J Dev Behav Pediatr. 2007 Apr;28(2):108-18.
  6. Hipskind SG, Henderson TA, Mena I. Position Paper: Reply to APA Council on children adolescents and their families on the use of NeuroSPECT in pediatric psychiatry. Alasbimn J. 2005 July 7(29): epub.
  7. DePaulo JR, Jr. Bipolar disorder treatment: an evidence-based reality check. 2006 Am J Psychiatry 163 (2): 175-176.
  8. Insel TR. Disruptive insights in psychiatry: Transforming a clinical discipline. 2009. Journal of Clinical Investigation 119 (4): 700–05.
  9. Lee JS, Kim BN, Kang E, Lee DS, Kim YK, Chung JK, Lee MC, Cho SC. Regional cerebral blood flow in children with attention deficit hyperactivity disorder: comparison before and after methylphenidate treatment. Hum Brain Mapp. 2005 Mar;24(3):157-64.
  10. Kim BN, Lee JS, Shin MS, Cho SC, Lee DS. Regional cerebral perfusion abnormalities in attention deficit/hyperactivity disorder. Statistical parametric mapping analysis. Eur Arch Psychiatry Clin Neurosci. 2002 Oct;252(5):219-25.
  11. Pliszka SR, Glahn DC, Semrud-Clikeman M, Franklin C, Perez R 3rd, Xiong J, Liotti M. Neuroimaging of inhibitory control areas in children with attention deficit hyperactivity disorder who were treatment naive or in long-term treatment. Am J Psychiatry. 2006 Jun;163(6):1052-60.
  12. Rubia K, Smith AB, Brammer MJ, Toone B, Taylor E. Abnormal brain activation during inhibition and error detection in medication-naïve adolescents with ADHD. Am J Psychiatry. 2005 Jun;162(6):1067-75.
  13. Cherkasova MV, Hechtman L. Neuroimaging in attention-deficit hyperactivity disorder: beyond the frontostriatal circuitry. Can J Psychiatry. 2009, Oct;54(10):651-64. 
  14. Mena I, Correa, R, Nader A, Boehme, V. Bipolar affective disorders: Assessment of functional brain changes by means of Tc-99m HMPAO NeuroSPECT. Alasbimn J. 2004 Jan 6(23):  epub.
  15. Bonte FJ, Weiner MF, Bigio EH, et al. Brain blood flow in the dementias: SPECT with histopathological correlation in 54 patients. Radiology 1997, 202(3):793-797.
  16. Jobst KA, Barnetson LP, Shepstone BJ. Accurate prediction of histologically confirmed Alzheimer's disease and the differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford Project to Investigate Memory and Aging. Int Psychogeriatr. 1998,10(3):271-302.
  17. Hanada K, Hosono M, Kudo T, Hitomi Y, Yagyu Y, Kirime E, Komeya Y, Tsujii N, Hitomi K, Nishimura Y. Regional cerebral blood flow in the assessment of major depression and Alzheimer's disease in the early elderly. Nucl Med Commun. 2006, Jun;27(6):535-41.
  18. Staffen W, Bergmann J, Schönauer U, Zauner H, Kronbichler M, Golaszewski S, Ladurner G. Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer's type: a semiquantitative and automated evaluation. Eur J Nucl Med Mol Imaging. 2009, May;36(5):801-10.
  19. Mayberg  HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron 2005, 45:651-660
  20. Amen, D, Highum, D, Licata, R, Annibali, J, Somner, L, Pigott, HE, Taylor, DV, Trujillo, M, Newberg, A, Henderson, T, Willeumier, K: Specific Ways Brain SPECT Imaging Enhances Clinical Psychiatric Practice, Specific Ways Brain SPECT Imaging Enhances Clinical Psychiatric Practice, Journal of Psychoactive Drugs, 2012, 44(2):96-106.
  21. Borghesani PR, DeMers SM, Manchanda V, Pruthi S, Lewis DH, Borson S. Neuroimaging in the clinical diagnosis of dementia: observations from a memory disorders clinic. J Am Geriatr Soc. 2010, Aug;58(8):1453-8.
  22. Ernst M, Freed ME, Zametkin AJ. Health hazards of radiation exposure in the context of brain imaging research: special consideration for children. J Nucl Med. 1998, Apr;39(4):689-98.
  1. Brockmann H et al. The value of HMPAO SPECT in predicting treatment response to citalopram in patients with major depression. Psychiatry Res. 2009, Aug 30;173(2):107-12.
  2. Amen DG, Stubblefield M, Carmicheal B, Thisted R. Brain SPECT findings and aggressiveness. Ann Clin Psychiatry. 1996, Sep;8(3):129-37.
  3. Yang Y, Glenn AL, Raine A. Brain abnormalities in antisocial individuals: implications for the law. Behav Sci Law. 2008, 26(1):65-83.
  4. Goethals I, Audenaert K, Jacobs F, Van den Eynde F, Bernagie K, Kolindou A, Vervaet M, Dierckx R, Van Heeringen C. Brain perfusion  SPECT in impulsivity-related personality disorders. Behav Brain Res. 2005, Feb 10;157(1):187-92.
  5. Miller BL, Darby A, Benson DF, Cummings JL, Miller MH. Aggressive, socially disruptive and antisocial behaviour associated with fronto-temporal dementia. Br J Psychiatry. 1997, Feb;170:150-4.
  6. Condray R, Morrow LA, Steinhauer SR, Hodgson M, Kelley M. Mood and behavioral symptoms in individuals with chronic solvent exposure. Psychiatry Res. 2000, Dec 27;97(2-3):191-206.
  7. Bowler RM, Mergler D, Rauch SS, Bowler RP. Stability of psychological impairment: two year follow-up of former microelectronics workers' affective and personality disturbance. Women Health. 1992, 18(3):27-48.
  8. Ginsberg Y, Hirvikoski T, Lindefors N. Attention Deficit Hyperactivity Disorder (ADHD) among longer-term prison inmates is a prevalent, persistent and disabling disorder. BMC Psychiatry. 2010 Dec 22;10:112
  9. Carlson GA, Potegal M, Margulies D, Gutkovich Z, Basile J. Rages-- what are they and who has them? J Child Adolesc Psychopharmacol. 2009, Jun;19(3):281-8.
  10. Amen DG, Stubblefield M, Carmicheal B, Thisted R. Brain SPECT findings and aggressiveness. Ann Clin Psychiatry. 1996, Sep;8(3):129-37.
  11. Storch EA, Jones AM, Lack CW, Ale CM, Sulkowski ML, Lewin AB, De Nadai AS, Murphy TK. Rage attacks in pediatric obsessive-compulsive disorder: phenomenology and clinical correlates. J Am Acad Child Adolesc Psychiatry. 2012, Jun;51(6):582-92.
  12. Holtmann M, Goth K, Wöckel L, Poustka F, Bölte S. CBCL-pediatric bipolar disorder phenotype: severe ADHD or bipolar disorder? J Neural Transm. 2008, 115(2):155-61.
  13. Hawley CA, Ward AB, Magnay AR, Long J. Outcomes following childhood head injury: a population study. J Neurol Neurosurg Psychiatry. 2004, May;75(5):737-42.
  14. Henderson TA, Hartman K. Aggression, mania, and hypomania induction associated with atomoxetine. Pediatrics. 2004, Sep;114(3):895-6.
  15. http://www.doseinfo-radar.com/RADARDoseRiskCalc.html
  16. http://www.epa.gov/rpdweb00/understand/calculate.html

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