Single Photon Emission Computerized Tomography (SPECT) scanning is a nuclear medicine technique. SPECT imaging can be used for many purposes depending on the tracer employed and is, in fact, one of the most commonly performed nuclear medicine tests in the world. Approximately, 8 million cardiac SPECT scans are performed annually using 99mTc-tetrafusmin (Myoview). Certain tracers allow the visualization of neurotransmitter receptors by SPECT scan. However, the much more commonscan is a brain perfusion SPECT, which is well-studied, and widely correlated with neuropsychiatric function. Brain blood flow is considered synonymous with brain function and has been since the 1800s.
In the 1980’s and 1990’s, radiolabeled Xenon was used for perfusion brain scans. It was plagued by low resolution due to the short half-life and need from rapid imaging. Initially, the resolution of the SPECT images was poor, making them difficult to interpret for clinical purposes. For many, these early images discredited the value of SPECT. However, over the years and driven by technological improvements, the resolution has improved dramatically. Being able to see where the brain function is low, normal, and high provides clinicians the opportunity to visualize brain (dys)function which may underlie psychiatric symptoms. In other words, through understanding how and where brain function is being disrupted, valuable clues can be gained as to the etiology of the symptoms and how they might be resolved.
Nowadays, two stable and long-lived tracers allow the visualization of brain perfusion (99mTc-HMPAO and 99mTc-ECD). Technological improvements in the gamma cameras, such as multi-headed cameras, tighter field of views, enhanced post-processing, and – more recently – the introduction of cadmium-zinc-telluride (CZT) solid state gamma detectors, have greatly improved the quality of SPECT scans. Resolution is now reliably at the 4.7 mm level and the CZT detector brings resolution down to 2.8 mm.
What 3-D brain SPECT scans show:
SPECT scans show areas of high blood flow, low blood flow, and normal blood flow and understanding where these different areas of blood flow occur allows us to determine how well these different parts of the brain are functioning. Traditionally nuclear medicine doctors looked at two-dimensional (2D) tomographic slices which are intimidating for most clinicians without training in the area. Technology has now advanced to the point where this data can be put into a three-dimensional (3D) image which resembles the shape of a brain. This is much more user-friendly for people who are not used to reading 2D tomographic slices. Below there is an example of some 2D tomographic slices and 3D images of a brain to illustrate the difference.
3-D SPECT :
Technology is user friendly,
Images correlate with clinical presentation
Images can help in choosing treatment.
Images can be used to evaluate treatment.
Images can be used to educate patients and therapists about psychiatric disorders and their treatment.
How to use brain SPECT scans:
Using brain SPECT scanning Imaging specialists (nuclear medicine, radiology) provide anatomical descriptions of blood flow in different parts of the brain. While this is very useful information, clinical correlation is always required. The nuclear medicine doctor cannot be expected to provide clinical interpretation or treatment recommendations as they do not have an intimate knowledge of the patient.
Physicians taking care of the patient can learn to combine the patient’s clinical information with SPECT scanning information from the Nuclear Medicine Doctor. Using imagery in this fashion helps to determine what parts of the brain are functioning normally, overworking or under functioning. This information can be useful as an aid to diagnosis and management.
How Functional Brain SPECT Scanning can help in the care of psychiatric patients
Brain blood flow SPECTs allow us to see brain function. Applying this information in a clinical settingcan help in the care of psychiatric patients. Physicians can learn to correlate imaging results (brain function) with clinical presentation. Whenphysicians share the SPECT scan findings with the patient,they can also correlate scan findings to clinical symptoms. When we look at brain function and correlate it with the patient’s symptomatology, it can give us further insight into how to help a patient. Patients usually find this very helpful, and it gives them a sense that their condition can be quantified and is real rather than “all in their heads”. In addition, the process of explaining the scan to a patient can often help the patient to remember previously undisclosed information. Our collective experience is that many diagnostic symptoms or clusters of symptoms correlate strongly with specific patterns of regional cerebral perfusion changes.
By the way, the dose of radiation from a SPECT scan is quite small – about 640 mRems – or equivalent to “a few airplane flights” (RADAR Home. Available at: http://www.doseinfo-radar.com/. Accessed January 31, 2017.).
Many Nuclear Medicine Doctors are not awarethat by looking at brain function they can have a role in helping in Psychiatry and helping psychiatric patients and their conditions. However, the truth is that Psychiatry is rooted in the brain. All that we think or feel and all that goes wrong in the ways that we think and feel occurs in the brain.
It has become increasingly unlikely that diagnoses as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) represent distinct neurophysiological entities. They will likely prove to represent groups of neurophysiological processes. Individual symptoms likely represent abnormal neurophysiological processes which span across diagnoses (e.g., impulsivity is a key component of the diagnosis of Impulse Control Disorder NOS, Attention-Deficit Hyperactivity Disorder {ADHD}, Bipolar mania, and certain personality disorders; but is also seen following frontal lobe injury, as in mild traumatic brain injury {TBI}, and in Frontal Temporal Dementia). So, it only follows that functional neuroimaging will fail to reveal a singular neurophysiological process corresponding in a one-to-one fashion with a DSM diagnosis. There is substantial evidence that there are multiple neurophysiological causes and imaging findings associated with conditions such as depression1-5, bipolar disorder6-9, ADHD10-23, autism24-28, and schizophrenia29,30. Yet, a brain-based understanding of psychiatric disorders remains an alien concept, scorned by much of the psychiatric community.
Neuroimaging is the way in which medical science looks at the brain. Anatomical imaging such as CT or MRI, allows us to look at the structure of the brain. These modalities can show tumors, bleeding, fractures, and degenerative changes in the late stage of dementia.
CT Scan
MRI Scan
But much as looking at a circuit board will not tell you if a computer will work, anatomical imaging (CT or MRI) contribute little to knowing if the brain is working properly. Functional brain imaging, such as Single Photon Computed Tomography (SPECT), Positron Emission Tomography (PET), and functional Magnetic Resonance Imaging (fMRI), allow you to examine brain function. These forms of imaging demonstrate how many parts of the brain are functioning, including critical areas like the temporal lobes and deep nuclei. Other modalities which are described as “scans”, such as qEEG, can only provide information about superficial areas of the cortex and provide no information about critical deep structures, such as the cingulate gyri, caudate nuclei, medial temporal lobes, and striatum.
Typical PET Scan – Alzheimer’s Disease
However, much of the focus in Psychiatry has been upon fMRI research. Decades of work and tens of millions of dollars have been spent on fMRI research with little definitive findings that identify an fMRI signature for a given psychiatric illness. It is important to understand the resolution of an fMRI scan and how poor the signal-to-noise ratio is. Below is the typical appearance of an fMRI scan. The large colored pixels are the fMRI data and they are overlayed on an anatomical MRI scan for anatomical reference.
Raw fMRI scan data
Bringing SPECT Scans Into Psychiatry – The Debate
In 2011, Dr. Henderson co-chaired a symposium at the American Psychiatric Association (APA) meeting entitled, The Pros and Cons of SPECT Brain Imaging in Psychiatry31. This was the first time in almost 10 years that SPECT brain imaging had been presented at the APA, reflecting a long-standing dismissal of SPECT by Psychiatry. At the symposium, the safety and potential clinical value of SPECT to address complex psychiatric diagnoses was presented. Dr. Michael Devous spoke concerning the technical aspects of SPECT and emphasized its value in evaluating the base of the brain because SPECT is free of artifact compared to CT or MRI. He also emphasized the value of SPECT in the evaluation of dementia wherein his own research has shown it to have a sensitivity of 89% and a specificity of 97%32. While critical of using SPECT for psychiatric illnesses, Dr. Devous clearly articulated the established indications of SPECT brain imaging, including stroke, seizures, traumatic brain injury (TBI – see link), and toxic brain injury.
Dr. Daniel Amen spoke about psychiatric applications of SPECT imaging, emphasizing that much of the time, SPECT is being used to ferret out undiagnosed TBI, toxic brain injury, partial complex seizures, and other neurological disorders that can masquerade as psychiatric disorders. He reviewed the relevant chapters of Morton’s textbook entitled Diagnostic Nuclear Medicine33 and Kaplan and Saddock’s Comprehensive Textbook of Psychiatry34, both of which state SPECT has considerable value in psychiatric indications. Dr. Amen discussed a recent study he and colleagues had completed wherein the charts of approximately 200 patients were assessed in a blind review by independent psychiatrists and a diagnosis was made. When the scan data was added to the clinical information, 75% of the cases had a change in diagnosis and indicated treatment.
In this debate, Dr. Henderson presented a scientific review of SPECT brain imaging. He began by emphasizing that SPECT scans are a form of medical test and, like all medical tests, has false negatives and false positives. Medicine accepts most other tests as “accurate”, despite the potential for false positives and false negatives; yet Psychiatry seems to hold neuroimaging to some higher standard. He further illustrated that imaging findings in radiology frequently yield multiple possible diagnoses. In Psychiatry, the situation is even more complicated, because patients often have multiple psychiatric diagnoses. This is further confounded by the fact that more than one kind of brain process can create a single psychiatric symptom – be it depression, anxiety, or inattention.
Dr. Henderson then explained the neurobiological underpinnings that allow us to visualize brain function with neuroimaging. He went on to explain the physics of PET, fMRI, and SPECT, emphasizing the strengths and weaknesses of each modality. In explaining SPECT, he underscored that SPECT and fMRI both looked at changes in perfusion as a way to assess brain function. Dr. Henderson moved on to discuss radiation safety. He illustrated the low level of radiation associated with a SPECT scan (about 0.7 rems) compared to other radiological studies and normal background radiation. He then numerous numerouslarge scale studies with over 100,000 subjects (mostly children) exposed to radiation doses 2-20 times higher than that received in a SPECT brain scan. Despite long-term follow-up for as much as 20 years, there was no long-term increased risk of cancer35.
Dr. Henderson pointed out the flaws in the APA position paper posted on their website in 2005, including the expectation of that psychiatric diagnoses occur in isolation – without comorbidity, the confusion between SPECT brain imaging providing supportive evidence for a diagnosis as opposed to “diagnosing” a psychiatric condition, and the expectation of a diagnostic fingerprint for each psychiatric condition. Moreover, he pointed out how the APA Position Paper confused the physics of SPECT and PET, exaggerated the risk of the associated radiation, and denied the existence of well-established normative databases. Of note, this position paper by the APA was withdrawn several years ago.
Dr. Henderson then reviewed key research studies demonstrating the efficacy of SPECT brain imaging in detecting TBI36-44, dementia45-48, obsessive-compulsive disorder49-54 (OCD), and ADHD10-23. He emphasized that TBI can often produce psychiatric symptoms. He emphasized that numerous SPECT studies and numerous fMRI studies of ADHD found identical results. He provided the audience with numerous research studies illustrating the same result – frontal cortex and orbitofrontal cortex perfusion decreases during concentration tasks in patients with ADHD (reviewed in reference 23). He provided two cases examples illustrating how SPECT brain imaging findings supported or mitigated against the diagnosis of ADHD.
Dr. Henderson built similar cases for bipolar disorder6-9 and for OCD49-54, demonstrating the SPECT research findings correlated with fMRI and PET findings leading to neurobiological processes which distinguish and identify ADHD, bipolar disorder, and OCD. Throughout, he illustrated with case examples of how SPECT brain imaging helped correctly identify the neurobiological processes in a patient and changed his/her treatment with markedly improved results.
Neuroimaging, including SPECT brain imaging, is a tool. It does not replace a careful psychiatric evaluation. Neuroimaging augments the evaluation. Neuroimaging shows us what the patient cannot tell us themselves about the brain trauma they did not think was important, the toxin exposure they may or may not know about, the brain infections they do not know they have, the disorder they have always been told is ADHD but is not, and the partial complex seizure disorder that leads them to behave in a bizarre manner at times.
References
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2. Savitz J, Drevets WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. NeurosciBiobehav Rev. 2009 May;33(5):699-771.
3. Savitz JB, Drevets WC. Imaging phenotypes of major depressive disorder: genetic correlates. Neuroscience. 2009 Nov 24;164(1):300-30.
4. Milak MS, Parsey RV, Lee L, Oquendo MA, Olvet DM, Eipper F, Malone K, Mann JJ. Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment. Psychiatry Res. 2009 Jul 15;173(1):63-70.
6. Benson BE, et al. Interregional cerebral metabolic associativity during a continuous performance task (Part II) : differential alterations in bipolar and unipolar disorders. Psychiatry Res. 2008 Oct 30;164(1):30-47.
7. 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.
8. Mena I. NeuroSPECT applications in psychiatry. Alasbimn J. 2009 July 11(45): epub
9. Pan L, et al., Functional neuroimaging studies of bipolar disorder: examining the wide clinical spectrum in the search for disease endophenotypes. Int Rev Psychiatry. 2009;21(4):368-79.
10. Gustafsson P, Thernlund G, Ryding E, Rosen I, Cederblad M. Associations between cerebral blood-flow measured by single photon emission computed tomography (SPECT), electro-encephalogram (EEG), behaviour symptoms, cognition and neurological soft signs in children with attention-deficit hyperactivity disorder (ADHD). Acta Paediatr. 2000 Jul;89(7):830-5.
11. Spalletta G, Pasini A, Pau F, Guido G, Menghini L, Caltagirone C. Prefrontal blood flow dysregulation in drug naive ADHD children without structural abnormalities. J Neural Transm. 2001;108(10):1203-16.
12. 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.
13. Langleben DD, Austin G, Krikorian G, Ridlehuber HW, Goris ML, Strauss HW. Interhemispheric asymmetry of regional cerebral blood flow in prepubescent boys with attention deficit hyperactivity disorder. Nucl Med Commun. 2001 Dec;22(12):1333-40.
14. Amen DG, Carmichael BD. High-resolution brain SPECT imaging in ADHD. Ann Clin Psychiatry. 1997 Jun;9(2):81-6.
15. Lorberboym M, Watemberg N, Nissenkorn A, Nir B, Lerman-Sagie T. Technetium 99m ethylcysteinate dimer single-photon emission computed tomography (SPECT) during intellectual stress test in children and adolescents with pure versus comorbid attention-deficit hyperactivity disorder (ADHD). J Child Neurol. 2004 Feb;19(2):91-6.
16. Smith AB, Taylor E, Brammer M, Toone B, Rubia K. Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder. Am J Psychiatry. 2006 Jun;163(6):1044-51.
17. 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.
18. Rubia K, Smith AB, Halari R, Matsukura F, Mohammad M, Taylor E, Brammer MJ. Disorder-specific dissociation of orbitofrontal dysfunction in boys with pure conduct disorder during reward and ventrolateral prefrontal dysfunction in boys with pure ADHD during sustained attention. Am J Psychiatry. 2009 Jan;166(1):83-94.
19. Rubia K, Halari R, Smith AB, Mohammad M, Scott S, Brammer MJ. Shared and disorder-specific prefrontal abnormalities in boys with pure attention-deficit/hyperactivity disorder compared to boys with pure CD during interference inhibition and attention allocation. J Child Psychol Psychiatry. 2009 Jun;50(6):669-78.
20. 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.
21. Durston S, Tottenham NT, Thomas KM, Davidson MC, Eigsti IM, Yang Y, Ulug AM, Casey BJ. Differential patterns of striatal activation in young children with and without ADHD. Biol Psychiatry. 2003 May 15;53(10):871-8.
22. Durston S, van Belle J, de Zeeuw P. Differentiating frontostriatal and fronto-cerebellar circuits in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2011 Jun 15;69(12):1178-84.
23. Cherkasova MV, Hechtman L. Neuroimaging in attention-deficit hyperactivity disorder: beyond the frontostriatal circuitry. Can J Psychiatry. 2009 Oct;54(10):651-64.
24. Burroni L, et al. Regional cerebral blood flow in childhood autism: a SPET study with SPM evaluation. Nucl Med Commun. 2008 Feb;29(2):150-6.
25. Ito H, et al., Findings of brain 99mTc-ECD SPECT in high-functioning autism–3-dimensional stereotactic ROI template analysis of brain SPECT. J Med Invest. 2005 Feb;52(1-2):49-56.
26. Pagani M, et al., Brief Report: Alterations in Cerebral Blood Flow as Assessed by PET/CT in Adults with Autism Spectrum Disorder with Normal IQ. J Autism Dev Disord. 2012 Feb;42(2):313-8.
27. Boddaert N, Zilbovicius M. Functional neuroimaging and childhood autism. PediatrRadiol. 2002 Jan;32(1):1-7.
28. Levitt JG, et al., Cerebellar vermis lobules VIII-X in autism. Prog Neuropsychopharmacol Biol Psychiatry. 1999 May;23(4):625-33.
29. Goghari VM, et al., The functional neuroanatomy of symptom dimensions in schizophrenia: a qualitative and quantitative review of a persistent question. NeurosciBiobehav Rev. 2010 Mar;34(3):468-86
30. Brown GG, Thompson WK. Functional brain imaging in schizophrenia: selected results and methods. Curr Top BehavNeurosci. 2010;4:181-214.
31. Henderson TA, Wu, J. Report on 2011 APA Symposium 24, Pros and Cons of SPECT Brain Imaging: What is the Status of the Science? – Presented May 15 2011 in Honolulu HI, submitted.
32. Devous MD Sr. Functional brain imaging in the dementias: role in early detection, differential diagnosis, and longitudinal studies. Eur J Nucl Med Mol Imaging. 2002 Dec;29(12):1685-96.
33. K. Morton et al., Diagnostic Nuclear Medicine, 1st edition. 2007, Elsevier.
34. 34. B. Saddock et al., Kaplan and Sadock’s Comprehensive Textbook of Psychiatry, 9th edition, 2009, Lippincott Williams & Wilkins.
35. 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
36. Ichise, M., Chung, D.G., Wang, P., Wortzman, G., Gray, B.G., & Franks, W. Technetium-99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic traumatic brain injury: A correlation with neuropsychological performance. Journal of Nuclear Medicine, 1994 34:217-226.
37. Kant, R, Smith-Seemiller, L., Isaac, G., & Duffy, J. Tc-HMPAO-SPECT in persistent post-concussion syndrome after mild head injury: comparison with MRI/CT. Brain Inj, 1997, 11(2):115-24.
38. Gowda NK, Agrawal D, Bal C, Chandrashekar N, Tripati M, Bandopadhyaya GP, Malhotra A, Mahapatra AK. Technetium Tc-99m ethyl cysteinate dimer brain single-photon emission CT in mild traumatic brain injury: a prospective study. AJNR Am J Neuroradiol. 2006 Feb;27(2):447-51.
39. Shin YB, Kim SJ, Kim IJ, Kim YK, Kim DS, Park JH, Yeom SR. Voxel-based statistical analysis of cerebral blood flow using Tc-99m ECD brain SPECT in patients with traumatic brain injury: group and individual analyses. Brain Inj. 2006 Jun;20(6):661-7.
40. Abu-Judeh HH, Parker R, Aleksic S, et al., SPECT brain perfusion findings in mild or moderate traumatic brain injury. JALASBIMN, 2(6), 2000. epub.
41. Jacobs, A., Put, E., Ingels, M, Bossuyt, A. Prospective Evaluation of Technetium-99m-HMPAO SPECT in Mild and Moderate Traumatic Brain Injury. J Nucl Med. 1994 35(6);947-8.
42. Jacobs, A., Put, E., Ingels, M. &Bossuyt, A. (1996). One-year follow-up of Technetium-99m-HMPAO SPECT in mild head injury. The Journal of Nuclear Medicine, 1996;37, 1605-1609.
43. Tatsch, K., Asenbaum, S., Bartenstein, P., Catafau, A., Halldin, C., Pilowsky, L.S., 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.
44. 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
45. Habert MO, Horn JF, Sarazin M, et al. Brain perfusion SPECT with an automated quantitative tool can identify prodromal Alzheimer’s disease among patients with mild cognitive impairment. Neurobiol Aging. 2011;32(1):15-23.
46. Pagani M, Salmaso D, Rodriguez G, et al. Principal component analysis in mild and moderate Alzheimer’s disease–a novel approach to clinical diagnosis. Psychiatry Res. 2009;173(1):8-14.
47. Chaves R, Ramírez J, Górriz JM, et al. SVM-based computer-aided diagnosis of the Alzheimer’s disease using t-test NMSE feature selection with feature correlation weighting. Neurosci Lett. 2009;461(3):293-7.
48. Matsuda H. Role of Neuroimaging in Alzheimer’s disease, with emphasis on brain perfusion SPECT. J Nucl Med. 2007;48(8):1289-300.
49. Lucey JV, Costa DC, Blanes T, Busatto GF, Pilowsky LS, Takei N, Marks IM, Ell PJ, Kerwin RW. Regional cerebral blood flow in obsessive-compulsive disordered patients at rest. Differential correlates with obsessive-compulsive and anxious-avoidant dimensions. Br J Psychiatry. 1995 Nov;167(5):629-34.
50. Saxena S, Brody AL, Ho ML, Alborzian S, Maidment KM, Zohrabi N, Ho MK, Huang SC, Wu HM, Baxter LR Jr. Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression. Arch Gen Psychiatry. 2002 Mar;59(3):250-61.
51. Diler RS, Kibar M, Avci A. Pharmacotherapy and regional cerebral blood flow in children with obsessive compulsive disorder. Yonsei Med J. 2004 Feb 29;45(1):90-9.
52. Rauch SL, Dougherty DD, Cosgrove GR, Cassem EH, Alpert NM, Price BH, Nierenberg AA, Mayberg HS, Baer L, Jenike MA, Fischman AJ. Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder. Biol Psychiatry. 2001 Nov 1;50(9):659-67.
53. Hoehn-Saric R, Pearlson GD, Harris GJ, Machlin SR, Camargo EE. Effects of fluoxetine on regional cerebral blood flow in obsessive-compulsive patients. Am J Psychiatry. 1991 Sep;148(9):1243-5.
54. Carey PD, Warwick J, Niehaus DJ, van der Linden G, van Heerden BB, Harvey BH, Seedat S, Stein DJ. Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram. BMC Psychiatry. 2004 Oct 14;4:30.
About SPECT
Single Photon Emission Computerized Tomography (SPECT) scanning is a nuclear medicine technique. SPECT imaging can be used for many purposes depending on the tracer employed and is, in fact, one of the most commonly performed nuclear medicine tests in the world. Approximately, 8 million cardiac SPECT scans are performed annually using 99mTc-tetrafusmin (Myoview). Certain tracers allow the visualization of neurotransmitter receptors by SPECT scan. However, the much more commonscan is a brain perfusion SPECT, which is well-studied, and widely correlated with neuropsychiatric function. Brain blood flow is considered synonymous with brain function and has been since the 1800s.
In the 1980’s and 1990’s, radiolabeled Xenon was used for perfusion brain scans. It was plagued by low resolution due to the short half-life and need from rapid imaging. Initially, the resolution of the SPECT images was poor, making them difficult to interpret for clinical purposes. For many, these early images discredited the value of SPECT. However, over the years and driven by technological improvements, the resolution has improved dramatically. Being able to see where the brain function is low, normal, and high provides clinicians the opportunity to visualize brain (dys)function which may underlie psychiatric symptoms. In other words, through understanding how and where brain function is being disrupted, valuable clues can be gained as to the etiology of the symptoms and how they might be resolved.
Nowadays, two stable and long-lived tracers allow the visualization of brain perfusion (99mTc-HMPAO and 99mTc-ECD). Technological improvements in the gamma cameras, such as multi-headed cameras, tighter field of views, enhanced post-processing, and – more recently – the introduction of cadmium-zinc-telluride (CZT) solid state gamma detectors, have greatly improved the quality of SPECT scans. Resolution is now reliably at the 4.7 mm level and the CZT detector brings resolution down to 2.8 mm.
What 3-D brain SPECT scans show:
SPECT scans show areas of high blood flow, low blood flow, and normal blood flow and understanding where these different areas of blood flow occur allows us to determine how well these different parts of the brain are functioning. Traditionally nuclear medicine doctors looked at two-dimensional (2D) tomographic slices which are intimidating for most clinicians without training in the area. Technology has now advanced to the point where this data can be put into a three-dimensional (3D) image which resembles the shape of a brain. This is much more user-friendly for people who are not used to reading 2D tomographic slices. Below there is an example of some 2D tomographic slices and 3D images of a brain to illustrate the difference.
3-D SPECT :
How to use brain SPECT scans:
Using brain SPECT scanning Imaging specialists (nuclear medicine, radiology) provide anatomical descriptions of blood flow in different parts of the brain. While this is very useful information, clinical correlation is always required. The nuclear medicine doctor cannot be expected to provide clinical interpretation or treatment recommendations as they do not have an intimate knowledge of the patient.
Physicians taking care of the patient can learn to combine the patient’s clinical information with SPECT scanning information from the Nuclear Medicine Doctor. Using imagery in this fashion helps to determine what parts of the brain are functioning normally, overworking or under functioning. This information can be useful as an aid to diagnosis and management.
How Functional Brain SPECT Scanning can help in the care of psychiatric patients
Brain blood flow SPECTs allow us to see brain function. Applying this information in a clinical settingcan help in the care of psychiatric patients. Physicians can learn to correlate imaging results (brain function) with clinical presentation. Whenphysicians share the SPECT scan findings with the patient,they can also correlate scan findings to clinical symptoms. When we look at brain function and correlate it with the patient’s symptomatology, it can give us further insight into how to help a patient. Patients usually find this very helpful, and it gives them a sense that their condition can be quantified and is real rather than “all in their heads”. In addition, the process of explaining the scan to a patient can often help the patient to remember previously undisclosed information. Our collective experience is that many diagnostic symptoms or clusters of symptoms correlate strongly with specific patterns of regional cerebral perfusion changes.
By the way, the dose of radiation from a SPECT scan is quite small – about 640 mRems – or equivalent to “a few airplane flights” (RADAR Home. Available at: http://www.doseinfo-radar.com/. Accessed January 31, 2017.).
Many Nuclear Medicine Doctors are not awarethat by looking at brain function they can have a role in helping in Psychiatry and helping psychiatric patients and their conditions. However, the truth is that Psychiatry is rooted in the brain. All that we think or feel and all that goes wrong in the ways that we think and feel occurs in the brain.
It has become increasingly unlikely that diagnoses as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) represent distinct neurophysiological entities. They will likely prove to represent groups of neurophysiological processes. Individual symptoms likely represent abnormal neurophysiological processes which span across diagnoses (e.g., impulsivity is a key component of the diagnosis of Impulse Control Disorder NOS, Attention-Deficit Hyperactivity Disorder {ADHD}, Bipolar mania, and certain personality disorders; but is also seen following frontal lobe injury, as in mild traumatic brain injury {TBI}, and in Frontal Temporal Dementia). So, it only follows that functional neuroimaging will fail to reveal a singular neurophysiological process corresponding in a one-to-one fashion with a DSM diagnosis. There is substantial evidence that there are multiple neurophysiological causes and imaging findings associated with conditions such as depression1-5, bipolar disorder6-9, ADHD10-23, autism24-28, and schizophrenia29,30. Yet, a brain-based understanding of psychiatric disorders remains an alien concept, scorned by much of the psychiatric community.
Neuroimaging is the way in which medical science looks at the brain. Anatomical imaging such as CT or MRI, allows us to look at the structure of the brain. These modalities can show tumors, bleeding, fractures, and degenerative changes in the late stage of dementia.
CT Scan
MRI Scan
But much as looking at a circuit board will not tell you if a computer will work, anatomical imaging (CT or MRI) contribute little to knowing if the brain is working properly. Functional brain imaging, such as Single Photon Computed Tomography (SPECT), Positron Emission Tomography (PET), and functional Magnetic Resonance Imaging (fMRI), allow you to examine brain function. These forms of imaging demonstrate how many parts of the brain are functioning, including critical areas like the temporal lobes and deep nuclei. Other modalities which are described as “scans”, such as qEEG, can only provide information about superficial areas of the cortex and provide no information about critical deep structures, such as the cingulate gyri, caudate nuclei, medial temporal lobes, and striatum.
Typical PET Scan – Alzheimer’s Disease
However, much of the focus in Psychiatry has been upon fMRI research. Decades of work and tens of millions of dollars have been spent on fMRI research with little definitive findings that identify an fMRI signature for a given psychiatric illness. It is important to understand the resolution of an fMRI scan and how poor the signal-to-noise ratio is. Below is the typical appearance of an fMRI scan. The large colored pixels are the fMRI data and they are overlayed on an anatomical MRI scan for anatomical reference.
Raw fMRI scan data
Bringing SPECT Scans Into Psychiatry – The Debate
In 2011, Dr. Henderson co-chaired a symposium at the American Psychiatric Association (APA) meeting entitled, The Pros and Cons of SPECT Brain Imaging in Psychiatry31. This was the first time in almost 10 years that SPECT brain imaging had been presented at the APA, reflecting a long-standing dismissal of SPECT by Psychiatry. At the symposium, the safety and potential clinical value of SPECT to address complex psychiatric diagnoses was presented. Dr. Michael Devous spoke concerning the technical aspects of SPECT and emphasized its value in evaluating the base of the brain because SPECT is free of artifact compared to CT or MRI. He also emphasized the value of SPECT in the evaluation of dementia wherein his own research has shown it to have a sensitivity of 89% and a specificity of 97%32. While critical of using SPECT for psychiatric illnesses, Dr. Devous clearly articulated the established indications of SPECT brain imaging, including stroke, seizures, traumatic brain injury (TBI – see link), and toxic brain injury.
Dr. Daniel Amen spoke about psychiatric applications of SPECT imaging, emphasizing that much of the time, SPECT is being used to ferret out undiagnosed TBI, toxic brain injury, partial complex seizures, and other neurological disorders that can masquerade as psychiatric disorders. He reviewed the relevant chapters of Morton’s textbook entitled Diagnostic Nuclear Medicine33 and Kaplan and Saddock’s Comprehensive Textbook of Psychiatry34, both of which state SPECT has considerable value in psychiatric indications. Dr. Amen discussed a recent study he and colleagues had completed wherein the charts of approximately 200 patients were assessed in a blind review by independent psychiatrists and a diagnosis was made. When the scan data was added to the clinical information, 75% of the cases had a change in diagnosis and indicated treatment.
In this debate, Dr. Henderson presented a scientific review of SPECT brain imaging. He began by emphasizing that SPECT scans are a form of medical test and, like all medical tests, has false negatives and false positives. Medicine accepts most other tests as “accurate”, despite the potential for false positives and false negatives; yet Psychiatry seems to hold neuroimaging to some higher standard. He further illustrated that imaging findings in radiology frequently yield multiple possible diagnoses. In Psychiatry, the situation is even more complicated, because patients often have multiple psychiatric diagnoses. This is further confounded by the fact that more than one kind of brain process can create a single psychiatric symptom – be it depression, anxiety, or inattention.
Dr. Henderson then explained the neurobiological underpinnings that allow us to visualize brain function with neuroimaging. He went on to explain the physics of PET, fMRI, and SPECT, emphasizing the strengths and weaknesses of each modality. In explaining SPECT, he underscored that SPECT and fMRI both looked at changes in perfusion as a way to assess brain function. Dr. Henderson moved on to discuss radiation safety. He illustrated the low level of radiation associated with a SPECT scan (about 0.7 rems) compared to other radiological studies and normal background radiation. He then numerous numerouslarge scale studies with over 100,000 subjects (mostly children) exposed to radiation doses 2-20 times higher than that received in a SPECT brain scan. Despite long-term follow-up for as much as 20 years, there was no long-term increased risk of cancer35.
Dr. Henderson pointed out the flaws in the APA position paper posted on their website in 2005, including the expectation of that psychiatric diagnoses occur in isolation – without comorbidity, the confusion between SPECT brain imaging providing supportive evidence for a diagnosis as opposed to “diagnosing” a psychiatric condition, and the expectation of a diagnostic fingerprint for each psychiatric condition. Moreover, he pointed out how the APA Position Paper confused the physics of SPECT and PET, exaggerated the risk of the associated radiation, and denied the existence of well-established normative databases. Of note, this position paper by the APA was withdrawn several years ago.
Dr. Henderson then reviewed key research studies demonstrating the efficacy of SPECT brain imaging in detecting TBI36-44, dementia45-48, obsessive-compulsive disorder49-54 (OCD), and ADHD10-23. He emphasized that TBI can often produce psychiatric symptoms. He emphasized that numerous SPECT studies and numerous fMRI studies of ADHD found identical results. He provided the audience with numerous research studies illustrating the same result – frontal cortex and orbitofrontal cortex perfusion decreases during concentration tasks in patients with ADHD (reviewed in reference 23). He provided two cases examples illustrating how SPECT brain imaging findings supported or mitigated against the diagnosis of ADHD.
Dr. Henderson built similar cases for bipolar disorder6-9 and for OCD49-54, demonstrating the SPECT research findings correlated with fMRI and PET findings leading to neurobiological processes which distinguish and identify ADHD, bipolar disorder, and OCD. Throughout, he illustrated with case examples of how SPECT brain imaging helped correctly identify the neurobiological processes in a patient and changed his/her treatment with markedly improved results.
Neuroimaging, including SPECT brain imaging, is a tool. It does not replace a careful psychiatric evaluation. Neuroimaging augments the evaluation. Neuroimaging shows us what the patient cannot tell us themselves about the brain trauma they did not think was important, the toxin exposure they may or may not know about, the brain infections they do not know they have, the disorder they have always been told is ADHD but is not, and the partial complex seizure disorder that leads them to behave in a bizarre manner at times.
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