Powerful Research Underlying Brain SPECT in Clinical Neuropsychiatric Practice

Compiled by Daniel G. Amen, MD

Below you will find a sample of articles on the use of brain SPECT imaging in clinical neuropsychiatric practice.  

Note, these are papers from:
JAMA,
Harvard Review of Psychiatry,
Radiology
Neuroimage
Neurology
Journal of Nuclear Medicine,
Journal of Clinical Psychiatry
General Hospital Psychiatry
Current Opinions in Neurology and Neurosurgery
Psychosomatics
Journal of Child Neurology
Radiological Clinics of   North America
European Journal of Nuclear Medical Molecular Imaging
Canadian Journal of Psychiatry
Journal of Clinical Neuroscience
Seminars in Nuclear Medicine

From places such as:
Harvard
Stanford
Columbia
University of Pennsylvania
University of Texas, Southwestern
St. Vincent’s Hospital in NY
University College and Middlesex School of Medicine, London, UK
University of Pittsburgh School of Medicine

From:
United States
UK
Canada
Spain
Brazil
Israel
Korea
Japan
Italy
Nigeria

They date from 1989 to 2008.

Single-photon emission computed tomography (SPECT). Applications and potential.

Holman BL, Tumeh SS.

JAMA. 1990 Jan 26;263(4):561-4.

Department of Radiology, Brigham and Women’s Hospital, Boston, MA 02115.

Single-photon emission computed tomography has received increasing attention as radiopharmaceuticals that reflect perfusion, metabolism, and receptor and cellular function have become widely available. Perfusion single-photon emission computed tomography of the brain provides functional information useful for the diagnosis and management of stroke, dementia, and epilepsy. Single-photon emission computed tomography has been applied to myocardial, skeletal, hepatic, and tumor scintigraphy, resulting in increased diagnostic accuracy over planar imaging because background activity and overlapping tissues interfere far less with activity from the target structure when tomographic techniques are used. Single-photon emission computed tomography is substantially less expensive and far more accessible than positron emission tomography and will become an increasingly attractive alternative for transferring the positron emission tomography technology to routine clinical use. In addition, single-photon emission computed tomography has unique applications that are increasingly finding their way into the routine practice of clinical nuclear medicine.

 

Contribution of neuroimaging in the prediction of outcome in neuropsychiatric disorders and learning disabilities

Kobayashi N, Kato M, Hoeft F

Brain Nerve 2007 Oct;59(10):1203-10

Center for Interdisciplinary Brain Science Research (CIBSR), Stanford University School of Medicine

Recent advances in cognitive neuroscience methods reveal the potential of neuroimaging as a useful tool in clinical and educational practice. In this review, we review the literature and provide evidence that functional and structural neuroimaging can detect changes with treatment. Further, we show promising initial results showing that the addition of neuroimaging measures can enhance conventional methods to predict outcome and prognosis. Examples are drawn from disorders such as attention-deficit / hyperactivity disorder (ADHD), depression, schizophrenia, obsessive-compulsive disorder (OCD), temporal lobe epilepsy, Alzheimer disease and developmental dyslexia. This evidence raises the intriguing possibility of utilizing neuroimaging data as a critical component in assessing and predicting cognitive abilities.

 

Single photon emission computed tomography in psychiatry: current perspectives.

Vasile RG.

Harv Rev Psychiatry, 4(1):27-38 1996 May-Jun.

Department of Psychiatry, Deaconess Hospital, Boston, MA

Single photon emission computed tomography (SPECT) is a widely available neuroimaging technique for the three-dimensional assessment of regional cerebral blood flow. The clinical utility of SPECT in neuropsychiatry is well established, and research devoted to its use in primary psychiatric disorders has been gaining momentum. In this review recent developments in SPECT neuroimaging are described, including the utility of SPECT in the differential diagnosis of the dementias and other neuropsychiatric conditions; SPECT studies of patients with affective disorders, at baseline and after treatment; and SPECT studies utilizing innovative techniques such as neuroreceptor imaging and activation strategies. Advances in SPECT research methodology and study design that may contribute to clarifying the pathophysiology of psychiatric disorders are examined.

 

Brain SPECT in clinical practice. Part I: perfusion

Catafau AM

J Nucl Med 2001 Feb;42(2):259-71

Nuclear Medicine Department, Autonomous University of Barcelona, Hospital de Sant Pau, Spain

Brain perfusion SPECT is a functional neuroimaging technique that allows noninvasive study of physiologic and physiopathologic events in the human brain. With the appropriate technique and careful interpretation of the information provided, brain perfusion SPECT has proven potential for patient management. SPECT has clinical value in the diagnosis, therapeutic management, and follow-up of patients. The diversity of central nervous system diseases and the still incomplete knowledge of the mechanisms that underlie them have contributed to the success of brain perfusion SPECT as a research tool in neurosciences. This article provides fundamental knowledge on how and when to perform brain perfusion SPECT in clinical practice. A general overview of the clinical value of this technique is followed by relevant information on cerebral physiology for proper understanding of brain SPECT images. Practical considerations on quantification and interventional studies are also offered. Finally, step-by-step recommendations for interpreting and reporting brain perfusion SPECT images are provided to obtain the maximum clinical benefit from this technique.

 

Brain SPECT in neurology and psychiatry.

Camargo EE

J Nucl Med 2001 Apr;42(4):611-23

Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas State University (Unicamp), Campinas, Brazil

Structural and functional images of the brain play an important role as powerful adjuncts in the management of an increasing number of neurologic and psychiatric diseases. Brain SPECT, in particular, with perfusion agents or with neuroreceptor imaging radiopharmaceuticals, is rapidly becoming a clinical tool in many places. For many neurologic and psychiatric conditions, this imaging modality has been used in diagnosis, prognosis assessment, evaluation of response to therapy, risk stratification, detection of benign or malignant viable tissue, and choice of medical or surgical therapy. The importance of this technique in nuclear medicine today should not be overlooked, particularly in cerebrovascular diseases, dementias, epilepsy, head injury, malignant brain tumors, movement disorders, obsessive-compulsive disorder, Gilles de la Tourette’s syndrome, schizophrenia, depression, panic disorder, and drug abuse.

 

Single photon emission computed tomography (SPECT) with [123I]IMP in the differential diagnosis of psychiatric disorders.

O’Connell RA, Van Heertum RL, et al.

J Neuropsychiatry Clin Neurosci 1989 Spring;1(2):145-53. Article Number: UI92330314

Department of Psychiatry, St. Vincent’s Hospital and Medical Center, New York, NY 10011

AB — Single photon emission computed tomography (SPECT) with [123I]N-isopropyl iodoamphetamine–[123I]IMP–was used to study regional cerebral blood flow (rCBF) in 94 psychiatric patients and six controls. Patients with dementias had distinct brain-image patterns, consistent with the expected neuropathology. Major depressives had decreased cortical and subcortical rCBF. Increased caudate rCBF was observed in schizophrenics and other psychoses with positive symptoms. SPECT is a practical method of functional brain imaging with potential in the differential diagnosis of neuropsychiatric disorders. Further studies are needed to assess the effect of other variables on brain-image patterns.

 

Studies of central nervous system disorders with single photon emission computed tomography and positron emission tomography: evolution over the past 2 decades. Review Article with 24 references.

Alavi A, Hirsch LJ:

Semin Nucl Med 1991 Jan;21(1):58-81

Radiology, Hospital of the University of Pennsylvania, Philadelphia 19104

AB – Single photon emission computed tomography (SPECT) was introduced in the 1960s to detect breakdowns in the blood-brain barrier and was replaced by x-ray computed tomography in the mid-1970s. The development of the deoxyglucose (DG) technique to measure regional cerebral glucose metabolism by employing either autoradiography, using 14CDG, or positron emission tomography (PET), using 18FDG, added a major dimension to the investigation of brain function. In the late 1970s and early 1980s, the FDG-PET technique was widely used to examine a variety of neuropsychiatric disorders. It soon became apparent that functional imaging was more sensitive than anatomic imaging in detecting abnormalities of the brain related to aging, dementia, tumors, seizures, cerebral vascular accidents, and psychiatric problems. Because of its complexity and the cost involved, PET was used in a limited number of centers in the United States. However, the success of PET resulted in the resurgence of interest in SPECT as an alternative technology after almost a decade. This became possible because of the synthesis of iodine 123- and technetium 99m-labeled radiopharmaceuticals to determine regional cerebral blood flow. Since blood flow and metabolism are coupled in most pathological states, patterns of abnormality noted on SPECT were similar to those seen on PET in many disorders. Since the introduction of high resolution SPECT imaging instruments, the role of SPECT has been further enhanced. The successful synthesis of both positron and single emitting radioligands to image dopamine and other receptors has started a new era in neurosciences and will have a far-reaching impact on the day-to-day practice of neuropsychiatry.

 

The role of SPECT brain imaging in assessing psychopathology in the medically ill.

O’Connell RA, Sireci SN Jr, Fastov et al.

Gen Hosp Psychiatry 1991 Sep;13(5):305-12.

Department of Psychiatry, St. Vincent’s Hospital, New York, NY

AB — Cerebral single photon emission computed tomography (SPECT), a method of functional brain imaging, measures cerebral blood flow and metabolism. This paper describes the imaging procedure and several cases where cerebral SPECT was of use in the differential diagnosis of medically ill patients who also presented with psychopathology. SPECT patterns in cerebrovascular disease, dementia, focal epilepsy, and AIDS are at present the best described and seem to be the most specific. Often changes in regional cerebral blood flow are seen before structural changes become apparent on CT or MRI. Cerebral SPECT can add valuable diagnostic information in assessing psychopathology in the medically ill and can often lead to changes in treatment.

 

The role of nuclear medicine in neurology and psychiatry.

Costa DC:

Curr Opin Neurol Neurosurg 1992 Dec;5(6):863-9

Institute of Nuclear Medicine, University College and Middlesex School of Medicine, London, UK

AB – Nuclear medicine has a place in the study of brain trauma, brain tumors, stroke, dementia epilepsy and depression. The development of new tracers labeled with widely available radionuclides, such as technetium-99m (99Tc) and iodine-123, has played a key role here. Practical methodology can now be implemented in the routine setting. Additional applications are reviewed in the context of brain death, encephalitis, post-viral fatigue syndrome, Parkinson’s disease and schizophrenia.

 

The relationship of SPECT scans to behavioral dysfunction in neuropsychiatric patients.

Trzepacz PT, Hertweck M, Starratt C, Zimmerman L, Adatepe MH:

University of Pittsburgh School of Medicine, PA

Psychosomatics 1992 Winter;33(1):62-71

AB — The authors describe 20 neuropsychiatric inpatients consecutively evaluated in the context of routine clinical care. Patients had both a neurological and psychiatric disorder. Each was clinically evaluated as part of a psychiatric hospitalization. DSM-III-R diagnoses, electroencephalograms, magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain, single photon emission computed tomography (SPECT) scans of the brain, and cognitive testing are reported. In only three cases were SPECT, MRI (or CT), and electroencephalogram all normal. SPECT abnormalities were associated with behavioral and cognitive presentations and with the hypothesized anatomical areas of dysfunction in 16 cases. In six cases SPECT and MRI were equivalent, involving structural lesions or normal scans. In only one case did MRI (or CT) detect deficits not revealed by SPECT, which were nonspecific white matter lesions and atrophy. The authors conclude that SPECT scans may be superior to structural brain scans in detecting clinically relevant deficits in neuropsychiatric patients, particularly when physiological lesions are involved.

 

Technetium 99mTc-HMPAO SPECT in children and adolescents with neurologic disorders.

Legido A, Price ML, Wolfson B, Faerber EN, Foley C, Miles D, Grover WD:

J Child Neurol 1993 Jul;8(3):227-34

Department of Pediatrics, St Christopher’s Hospital for Children, Philadelphia, PA 19134

AB — We evaluated regional cerebral blood flow with technetium 99mTc HMPAO single photon emission computed tomography (SPECT) in 20 children and adolescents with neurologic dysfunction of varied etiology and abnormal electroencephalograms (EEGs). All patients were also examined with computed tomography (CT) and magnetic resonance imaging (MRI). Abnormal perfusion was found in 17 (85%) of 20 SPECT scans. Abnormal CT or MRI scans were noted in nine (45%) and in 10 (50%) of 20 cases, respectively. In eight (73%) of 11 cases with normal CT scans and in seven (70%) of 10 with normal MRI scans, the SPECT scan was abnormal. Abnormal regional cerebral blood flow on SPECT scans correlated better with EEG abnormalities than with neurologic examination or CT or MRI scan findings. We conclude that in children and adolescents with a spectrum of neurologic diseases and abnormal EEGs, abnormalities of brain structure or function are more likely to be documented by SPECT than by CT or MRI scans. SPECT findings correlate well with the location and type of EEG abnormality.

 

SPECT brain imaging in neurologic disease.

Van Heertum RL, Miller SH, Mosesson RE:

Radiol Clin North Am 1993 Jul;31(4):881-907

Department of Radiology, Columbia-Presbyterian Medical Center, New York, NY 10032

AB – In recent years cerebral SPECT imaging is rapidly evolving as a clinical tool in the evaluation of a variety of neurologic disorders. In large part, the major advances in brain imaging which have occurred in the last four years are related to new developments in instrumentation and radiopharmaceuticals. In particular, the increased availability of multidetector and dedicated ring detector systems has given rise to improved image resolution and more rapid patient throughput. Advances in the field of radiopharmaceutical development, particularly as it pertains to perfusion brain SPECT agents, has also contributed to the advances in the field. As a result of these developments, there has been an expanded interest in and use of brain SPECT imaging procedures in the evaluation of cerebrovascular disease, dementia, epilepsy, and head trauma.

 

Brain imaging and its clinical application in psychiatry.

Hendler T; Gross R; Goshen E; Faibel M; Hirshmann S; Zwass TS; Grunhaus L; Zohar J.

Harefuah, 133(9):337-42, 416 1997 Nov 2

Psychiatry Unit, Chaim Sheba Medical Center, Tel Hashomer

The common structural and functional brain imaging techniques are described from a practical, clinical point of view. The clinical indications for brain imaging in psychiatry are reviewed in relation to the specific limitations and advantages of each technique. The clinical applications of computerized tomography (CT), magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT) are discussed in relation to the differential diagnosis between organic and functional psychiatric disorders. In a 55-year-old man with late onset of behavioral changes but without neurological signs the application of structural brain imaging (CT and MRI) in case management was demonstrated. The imaging findings involved the differential diagnosis between depression and focal brain lesions. In a 38-year-old man with personality changes and depression following a traumatic brain injury, time interval repeated functional brain imaging (SPECT) was used. Brain imaging reflected improvement in clinical status following treatment and was able to differentiate between reversible and permanent traumatic brain injuries. The superior yield of time interval repeated functional imaging in diagnosis and management of postconcussion syndrome is discussed.

 

Effect of lamotrigine on cerebral blood flow in patients with idiopathic generalized epilepsy

Joo EY, Hong SB, Tae WS, Han SJ, Seo DW, Lee KH, Lee MH

Eur J Nucl Med Mol Imaging. 2006 Mar 10

Department of Neurology, College of Medicine, Ewha Womans University,, Seoul, Korea

PURPOSE: The purpose of this study was to investigate the effects of the new anti-epileptic drug, lamotrigine, on cerebral blood flow by performing (99m)Tc-ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) before and after medication in patients with drug-naive idiopathic generalised epilepsy. METHODS: Interictal (99m)Tc-ECD brain SPECT was performed before drug treatment started and then repeated after lamotrigine medication for 4-5 months in 30 patients with generalised epilepsy (M/F=14/16, 19.3+/-3.4 years). Seizure types were generalised tonic-clonic seizure in 23 patients and myoclonic seizures in seven. The mean lamotrigine dose used was 214.1+/-29.1 mg/day. For SPM analysis, all SPECT images were spatially normalised to the standard SPECT template and then smoothed using a 12-mm full-width at half-maximum Gaussian kernel. The paired t test was used to compare pre- and post-lamotrigine SPECT images. RESULTS: SPM analysis of pre- and post-lamotrigine brain SPECT images showed decreased perfusion in bilateral dorsomedial nuclei of thalami, bilateral uncus, right amygdala, left subcallosal gyrus, right superior and inferior frontal gyri, right precentral gyrus, bilateral superior and inferior temporal gyri and brainstem (pons, medulla) after lamotrigine medication at a false discovery rate-corrected p<0.05. No brain region showed increased perfusion after lamotrigine administration. CONCLUSION: Our study demonstrates for the first time the effect of lamotrigine on interictal cerebral perfusion in drug-naive idiopathic generalised epilepsy patients. In summary, lamotrigine medication was found to reduce perfusion in cortico-thalamo-limbic areas, the orbitofrontal cortex, and brainstem.

 

PET and SPECT imaging in psychiatric disorders

Zipursky RB, Meyer JH, Verhoeff NP

Can J Psychiatry 2007 Mar;52(3):146-57

Department of Psychiatry and Behavioural Neurosciences, Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario

OBJECTIVES: To review recent findings from positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies that investigate the pathophysiology and treatment of schizophrenia, depression, and dementia. METHODS: We carried out a review of the literature. RESULTS: PET and SPECT studies have provided evidence of dopamine system dysregulation in patients with schizophrenia and variable loss of monoamines in patients with depression. Antipsychotic response has been demonstrated to be associated with blockade of dopamine D2 receptors, and antidepressant response has now been linked to blockade of serotonin transporter receptors. PET and SPECT have been extensively evaluated as diagnostic procedures for dementia. Substantial progress has been made in developing radioligands that bind to amyloid deposits in the brain, which should provide new opportunities for early diagnosis and treatment monitoring in Alzheimer’s disease. CONCLUSION: Advances in PET and SPECT imaging have provided new insights into the biology of major psychiatric disorders and their treatment. In the future, we can expect that these imaging techniques will become more central to the management of psychiatric disorders.

 

The relationship between cerebral blood flow and cognitive function in patients with brain insult of various etiology

Shiraishi H, Chang CC, Kanno H, Yamamoto I

J Clin Neurosci 2004 Feb;11(2):138-41

Department of Neurosurgery, Yokohama University School of Medicine, Yokohama, Japan

The relationship between the mean cerebral blood flow (CBF) and cognitive function was investigated in patients with brain insult. This study included 72 patients aged 24-85 years treated for the following diseases: cerebral infarction (21), intracerebral hemorrhage (4), subarachnoid hemorrhage (2), brain tumor (14), cerebral contusion (12), normal pressure hydrocephalus (13), Alzheimer’s disease (2), and others (4). First-pass radionuclide angiography using Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was performed for the measurement of the mean CBF, and the Sturb-Black Mental Status Examination for the neuropsychological evaluation. The mean CBF and the score of the neuropsychological test were significantly reduced compared with those of the age-matched controls. Regardless of etiology, the mean CBF and the score of neuropsychological test were significantly reduced, and a significant correlation was observed except for the patients with cerebral contusion. The quantitative measurement of CBF using 99mTc-HMPAO is reliable to estimate the neuropsychological state.

 

Clinical brain radionuclide imaging studies.

Messa C, Fazio F, Costa DC, Ell PJ:

Semin Nucl Med 1995 Apr;25(2):111-43

University of Milan, S. Raffaele Institute, Italy

AB – A recent survey of the knowledge and practice of both positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) of the brain among referring physicians in Europe (neurologists and psychiatrists) showed a disquieting lack of knowledge of the potential of these methodologies in the investigation and management of patients of their own specialities. The need to bring the knowledge of the potential of these techniques to the practicing physicians is paramount. It is imperative that the methodologies and concepts that preside over the application of these techniques in neurology and psychiatry must become more uniform if an impact is to be felt at a clinical level. There is clear improvement in the instrumentation available with the new state-of-the-art tomographic devices and with the development of new technetium-based radiopharmaceuticals for the study of cerebral perfusion. The constant progress made with ligands that permit the study of neurotransmission, tumor metabolism, and turnover do expand our capability to improve the knowledge concerning neurophysiology, neuropathology, and neuropharmacology of a variety of disease states. PET and SPECT will be progressively included in protocols aimed at stratifying patients with dementia, monitoring therapeutic trials, and improving our ability to determine outcome. Clinical usefulness of PET and SPECT begin to emerge in cerebral vascular disease, in the identification of cerebral death, in epilepsy, in cerebral trauma, in the investigation of HIV-positive patients with cerebral involvement, and in the monitoring of tumor recurrence and postirradiation damage. This review article outlines a current perspective of SPECT and PET as practiced in Europe, its potential, and its limitations.

 

Brain mapping with single photon emission CT.

Matthew E; Hill TC.

Radiology, 206(2):483-9 1998 Feb.

Department of Radiologic Sciences, Beth Israel Deaconess Medical Center-West Campus, Harvard Medical School, Boston, MA

PURPOSE: To investigate the feasibility of performing brain mapping studies by using cortical activation paradigms and single photon emission computed tomography (SPECT) and to evaluate methods of analysis.
MATERIALS AND METHODS: Twenty healthy volunteers underwent technetium-99m bicisate SPECT under baseline conditions and during either full-field or right hemifield visual stimulation with a black and white reversing checkerboard pattern. Changes in regional cerebral perfusion were measured by using regions of interest (ROIs) and statistical parametric mapping.
RESULTS: ROI analysis identified statistically significant increases in perfusion in the occipital cortex with full-field visual stimulation (mean +/- standard error of the mean percentage change from baseline: left, 8.0 +/- 1.5; right, 6.6 +/- 2.4). With right hemifield visual stimulation, perfusion was significantly increased only in the left occipital cortex (left, 5.2 +/- 1.5; right, -0.2 +/- 1.9). Statistical parametric mapping showed areas of activation (more than 100 voxel clusters showed significant change from baseline at a threshold value of P < or = .005 or z > or = 2.58) in the left primary visual cortex (right hemifield visual stimulation) and in both right and left primary visual areas (full-field visual stimulation).
CONCLUSION: Brain mapping studies were preformed with Tc-99m bicisate SPECT, and activation-induced changes were visualized and measured. These methods can be applied to develop improved methods of diagnosis and assessment of treatment outcome in patients with neuropsychiatric disorders.

 

Role of radiology in psychiatry: a review

Abiodun, OA

East Afr Med J. 2005 May;82(5):260-6.

Department of Behavioural Sciences, College of Medicine, University of Ilorin, Ilorin, Nigeria.

OBJECTIVE: To assess the contributions of radiological studies to current level of understanding of the pathophysiological mechanisms that underlie psychiatric symptoms/ disorders and their treatment. DATA SOURCES: Published articles in indexed journals. STUDY SELECTION: Radiological studies of psychiatric populations with emphasis on neuroimaging techniques. DATA EXTRACTION: Information concerning aetiological factors, pathophysiological mechanisms and treatment of psychiatric disorders were scrutinized. DATA SYNTHESIS: Structural changes on CT, in schizophrenia include enlargement of the ventricles, cerebral sulci and fissure. MRI studies in these patients confirm significant differences in ventricular volume and medial temporal structures. Functional changes on PET, SPECT and fMRI in depressed patients include altered cerebral blood flow and metabolism in the pre-frontal cortex, anterior cingulate, caudate nucleus, amygdala and thalamus, suggesting abnormal interactions in several brain regions. Drug distribution can be imaged by MRS and this has shown brain lithium level to be about half the plasma level. PET and SPET studies have demonstrated that unlike the classical antipsychotics (e.g. chlorpromazine), atypical antipsychotic drugs such as risperidone and clozapine have high cortical serotonin (5HT2) receptor occupancy (80-90%), thus challenging the theory of a simple relationship between dopamine (D2) receptor occupancy (blocked by classical antipsychotics) and clinical efficacy. CONCLUSION: Radiological studies of psychiatric populations add to available knowledge on the biological aspects of psychiatry. It is therefore essential to provide and update radiological facilities in mental health institutions in developing countries.

 

Prediction of psychiatric response to donepezil in patients with mild to moderate Alzheimer’s disease.

Tanaka M, Namiki C, Thuy DH, Yoshida H, Kawasaki K, Hashikawa K, Fukuyama H, Kita T.

J Neurol Sci. 2004 Oct 15;225(1-2):135-41.

Department of Social Service, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Donepezil is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderate Alzheimer’s disease (AD). Since behavioral symptoms severely affect quality of life for AD patients and their caregivers, predicting behavioral responses to donepezil will be useful in managing patients with AD. In this study, we analyzed 70 consecutive cases with mild to moderate AD. Caregivers were interviewed with the Neuropsychiatric Inventory for behavioral assessment and 4-point improvement at week 12 was accepted as a treatment response. Twenty-one (30.0%) patients showed a behavioral response, while 42 (60.0%) showed no behavioral change and 7 (10.0%) worsened. Dysphoria, anxiety and apathy significantly improved after treatment among the responder group. The baseline profile including age, sex, Mini-Mental State Examination (MMSE), the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Geriatric Depression Scale did not differ significantly among the three groups. Statistical Parametric Mapping analysis of single photon emission computed tomography (SPECT) images at baseline showed that cerebral blood flow in the premotor and parietotemporal cortices was significantly higher in the responder group than in the worse group. The present study suggested usefulness of SPECT imaging in the prediction of behavioral response to donepezil among AD patients even with similar psychiatric symptoms and cognitive functions.

Neuroimage. 2005 Dec;28(4):1014-21. Epub 2005 Aug 29.

  
The prediction of rapid conversion to Alzheimer’s disease in mild cognitive impairment using regional cerebral blood flow SPECT.

Hirao K, Ohnishi T, Hirata Y, Yamashita F, Mori T, Moriguchi Y, Matsuda H, Nemoto K, Imabayashi E, Yamada M, Iwamoto T, Arima K, Asada T.

Department of Radiology, National Center Hospital of Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, Tokyo, Japan.

Mild cognitive impairment (MCI) comprises a heterogeneous group with a variety of clinical outcomes and they are at risk for developing Alzheimer’s disease (AD). The prediction of conversion from MCI to AD using the initial neuroimaging studies is an important research topic. We investigated the initial regional cerebral blood flow (rCBF) measurements using single photon emission computed tomography (SPECT) in individuals with 76 amnesic MCI (52 subjects converted to AD and 24 subjects did not convert to AD at 3-year follow-up) and 57 age- and gender-matched controls. We sought functional profiles associated with conversion to AD, then evaluated the predictive value of the initial rCBF SPECT. As compared with controls, AD converters demonstrated reduced blood flow in the bilateral parahippocampal gyri, precunei, posterior cingulate cortices, bilateral parietal association areas, and the right middle temporal gyrus. Non-converters also demonstrated significant reduction of rCBF in the posterior cingulated cortices and the right caudate nucleus when compared to controls. As compared with non-converters, converters showed reductions of rCBF in the bilateral temporo-parietal areas and the precunei. The logistic regression model revealed that reduced rCBF in the inferior parietal lobule, angular gyrus, and precunei has high predictive value and discriminative ability. Although a cross-validation study is needed to conclude the usefulness of rCBF SPECT for the prediction of AD conversion in individuals with MCI, our data suggest that the initial rCBF SPECT studies of individuals with MCI may be useful in predicting who will convert to AD in the near future.

 

Brain perfusion imaging predicts survival in Alzheimer’s disease.

Jagust WJ, Haan MN, Reed BR, Eberling JL.
Neurology. 1998 Oct;51(4):1009-13.
The Center for Functional Imaging, Lawrence Berkeley National Laboratory, and the Department of Neurology, University of California, Davis 94720, USA.
BACKGROUND: The variability of disease course in patients diagnosed with AD makes prediction of survival difficult, despite the identification of numerous predictors to date. This study evaluated the predictive utility of measurements of regional cerebral blood flow (rCBF) obtained with SPECT in a group of AD patients. METHODS: Fifty AD patients were studied with SPECT and followed longitudinally. SPECT measures of relative rCBF were calculated by measuring radioactivity densities in dorsolateral frontal, orbitofrontal, temporal, and parietal cortex normalized to occipital cortical radioactivity density. Subjects were classified into three tertiles of rCBF ratios for each region. These rCBF ratios were used as predictors of survival in life-table and proportional hazard models to predict survival. RESULTS: Right parietal rCBF was a significant predictor of survival in the life-table analysis, with subjects in the lowest tertile having shortest survivals. No other brain region was a significant predictor of survival. In a proportional hazards model when a variety of other potential predictors were accounted for, right parietal rCBF ratio remained a significant predictor. CONCLUSIONS: These results demonstrate that brain perfusion in the right parietal lobe is a significant predictor of survival in patients with AD even when other predictors are taken into consideration. This suggests that SPECT perfusion imaging may provide additional useful information on disease prognosis in AD.

 

Functional brain SPECT: the emergence of a powerful clinical method.

Holman BL, Devous MD Sr.

J Nucl Med. 1992 Oct;33(10):1888-904.

AB — Single-photon emission computed tomography (SPECT) techniques provide a powerful window into the function of the brain and promise to become an important component of the routine clinical evaluation of patients with neurological and psychiatric diseases. While it initially appeared that brain SPECT would suffer from a number of limitations relative to positron emission tomography (PET), recent improvements in instrumentation and radiopharmaceuticals as well as increasingly compelling clinical evaluations suggest a primary role for SPECT in the diagnosis of a number of highly prevalent neurological diseases. SPECT imaging, even with high-resolution systems, is substantially less expensive than PET and is more widely available. Furthermore, a number of novel approaches to diagnosis have been developed for SPECT exclusively. The implementation of this method into clinical practice has been slow, however, and its appropriate utilization will require much closer collaboration between nuclear medicine physicians, neurologists, psychiatrists and neurosurgeons.