Cerebral perfusion imaging in Alzheimer's disease. Use of single photon emission computed tomography and iofetamine hydrochloride I 123

We used single photon emission computed tomography (SPECT) to study 15 patients with Alzheimer's disease and nine controls. Iofetamine hydrochloride I 123 uptake data were recorded from the entire brain using a rotating gamma camera. Activity ratios were measured for the frontal, posterior parietal, posterior, medial, and lateral cortical temporal regions and striate cortex and were normalized by the activity in the cerebellum. Abnormalities in iofetamine hydrochloride I 123 activity were similar to the abnormalities in glucose metabolism observed with positron emission tomography. Cortical tracer activity was globally depressed in patients with Alzheimer's disease, with the greatest reduction in the posterior parietal cortex.     

The diagnosis of dementia with single photon emission computed tomography

Single photon emission computed tomography is a practical modality for the study of physiologic cerebral activity in vivo. We utilized single photon emission computed tomography and N-isopropyl-p-iodoamphetamine iodine 123 to evaluate regional cerebral blood flow in nine patients with Alzheimer's disease (AD), five healthy elderly control subjects, and two patients with multi-infarct dementia. We found that all subjects with AD demonstrated flow deficits in temporoparietal cortex bilaterally, and that the ratio of activity in bilateral temporoparietal cortex to activity in the whole slice allowed the differentiation of all patients with AD from both the controls and from the patients with multi-infarct dementia. Furthermore, this ratio showed a strong correlation with disease severity in the AD group. Single photon emission computed tomography appears to be useful in the differential diagnosis of dementia and reflects clinical features of the disease.     

Unilateral spatial neglect in Alzheimer's disease A line bisection study

Neuropsychological studies on Alzheimer's disease (AD) have rarely mentioned about unilateral spatial neglect in spite of widespread use of visuospatial tasks. We reported a 62-year-old woman with probable AD who showed moderate dementia with left unilateral spatial neglect and relatively preserved language function. An extensive line bisection study with either hand confirmed her having left unilateral spatial neglect. Single photon emission computed tomography revealed relative hypoperfusion in the right temporal and parietal regions. AD patients with disproportionate right hemisphere dysfunction may exhibit left unilateral spatial neglect if tested adequately in the stage of mild to moderate dementia. We consider that application of the line bisection test to AD patients contributes to estimation of their right hemisphere function.     

Statistical parametric mapping of brain SPECT perfusion abnormalities in patients with Alzheimer's disease

Brain perfusion in 20 patients with mild Alzheimer's disease (AD), 20 patients with moderate AD and 20 control subjects (matched for age, gender and education) were assessed by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO). SPECT images were transformed to a standard size and shape for group comparisons by the voxel-based t test of the statistical parametric mapping techniques. Cerebral hypoperfusion in the left lower parietal area was found in mild AD patients. In moderate AD patients, significant cerebral hypoperfusion was located in bilateral posterior parietotemporal cortices, contiguous anterior occipital lobes, posterior cingulate gyri and, to a lesser extent, in frontal areas.     

A high-resolution single photon emission computed tomography study of verbal recognition memory in Alzheimer's disease

BACKGROUND: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer's disease (AD) subjects on a verbal recognition memory task. METHODS: Eighteen early AD and 10 matched healthy control subjects underwent split-dose (99m)Tc-HMPAO (Ceretec) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. RESULTS: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. CONCLUSIONS: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.     

SPECT imaging of serotonin2 receptors in depression.

Changes of serotonin2 (5HT2) receptors have been described in depression, and long-term antidepressant treatment has been shown to decrease the number of 5HT2 receptors. In this study, single photon emission computed tomography (SPECT), with 2-123I-ketanserin as a ligand, was used to investigate 5HT2 receptors in vivo in the brain of depressed patients and normal volunteers. A higher uptake of the tracer was observed in the parietal cortex of the patients, and there was a right greater than left asymmetry in the infero-frontal region of the depressed subjects and not in that of the control subjects. These findings could indicate changes in 5HT2 receptors in major depression.     

Assessment of neuroinflammation and microglial activation in Alzheimer's disease with radiolabelled PK11195 and single photon emission computed tomography. A pilot study

OBJECTIVES: Inflammation contributes to degeneration in Alzheimer's disease (AD), not simply as a secondary phenomenon, but primarily as a significant source of pathology. [(123)I]iodo-PK11195 is a single photon emission computed tomography (SPECT) ligand for the peripheral benzodiazepine receptor, the latter being expressed on microglia (brain resident macrophages) and upregulated under inflammatory circumstances. The objectives were to assess AD inflammation by detecting [(123)I]iodo-PK11195 uptake changes and investigate how uptake values relate with perfusion SPECT and neuropsychological findings. METHODS: Ten AD and 9 control subjects were included. [(123)I]iodo-PK11195 SPECT images were realigned into stereotactic space where binding indices, normalized on cerebellar uptake, were calculated. RESULTS: The mean [(123)I]iodo-PK11195 uptake was increased in AD patients compared with controls in nearly all neocortical regions; however, statistical significance was only reached in the frontal and right mesotemporal regions. Significant correlations were found between regional increased [(123)I]iodo-PK11195 uptake and cognitive deficits. CONCLUSIONS: [(123)I]iodo-PK11195 is a cellular disease activity marker and allows in vivo assessment of microglial inflammation in AD.     

Single-Photon Emission Computed Tomographic Perfusion Imaging in Autopsy-Diagnosed Dementia

Physiological imaging of regional cerebral blood flow with single-photon emission computed tomography (SPECT) has been proposed to be diagnostically useful in the evaluation of patients with dementia because of the frequent finding of temporal and parietal lobe hypoperfusion in patients with Alzheimer's disease (AD). A major limitation of SPECT to date has been the selection of patients using clinical criteria, which may be unreliable in excluding patients with non-Alzheimer dementias from study. SPECT with the perfusion tracer ¹²³l-N-isopropyl-p-iodoamphetamine was used to study 16 dementia patients who were subsequently followed to autopsy, as well as 16 elderly control subjects. Eleven dementia patients had the diagnosis of AD confirmed by autopsy, while 5 had other, nonAD dementias. SPECT perfusion patterns were evaluated as regional ratios of lobar radioactivity counts normalized to either activity counts in the occipital lobes (occipital ratio) or activity counts in the entire tomographic slice (whole-slice ratio). Results showed that the relative frontal perfusion differentiated non-AD patients from control subjects and AD patients regardless of which ratio method was used, while temporal and parietal relative perfusion ratios were more effective at differentiating AD from non-AD patients when the whole-slice ratio was used, although the ratio used did not affect the differentiation of AD patients from control subjects. Scatterplots of the whole-slice ratio in the right parietal and left temporal lobes showed no overlap between AD and non-AD patients and control subjects. These results support the diagnostic utility of SPECT in the clinical evaluation of dementia patients, particularly in distinguishing AD from non-AD dementias during life.     

Frontal assessment battery and brain perfusion image in Parkinson's disease

The objective was to compare brain perfusion image using 3-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between Parkinson's disease patients with a high frontal assessment battery score and those with a low frontal assessment battery score. Thirty nondemented patients with Parkinson's disease were studied. Patients were divided into 2 groups: a high-scoring group whose frontal assessment battery score was 12 or more and a low-scoring group whose frontal assessment battery score was 11 or less. The high-scoring group included 21 patients, and the low-scoring group included 9 patients. They underwent N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography, and we analyzed the data by the 3-dimensional stereotactic surface projection method. Results showed that left inferior parietal lobule and left supramarginal gyrus perfusion of the low-scoring group were significantly decreased compared with the high-scoring group. It is concluded that patients with Parkinson's disease may have frontal lobe dysfunction, but the decreased frontal assessment battery score may be caused not by progressed frontal lobe dysfunction but by parietal lobe dysfunction added to their preexisting frontal lobe impairment.     

Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease

Regional CMRglc (rCMRglc) values were determined with positron emission tomography (PET) in 10 patients with mild to moderate clinically diagnosed Alzheimer's disease (AD) and in 26 healthy controls. rCMRglc in frontal, parietal, and temporal association cortices were significantly more laterally asymmetrical in AD patients than in controls (p less than 0.05). Furthermore, lateral asymmetry of rCMRglc in AD patients but not in the control subjects correlated significantly with asymmetry of language and visuospatial functions such that lower left than right rCMRglc was associated with relatively greater impairment of language and vice versa. The results demonstrate that discrepancies between language and visuospatial deficits in patients with early AD are related to asymmetrical reductions in cerebral cortical glucose metabolism.     

Neural substrates for writing impairments in Japanese patients with mild Alzheimer's disease: a SPECT study

Language is fairly well preserved in most patients with mild Alzheimer's disease, but writing ability seems to be impaired even in the early stages of the disease. To investigate the neural bases of writing impairments in Alzheimer's disease (AD), we examined the correlation between writing ability and regional cerebral blood flow (rCBF) in 52 Japanese patients with mild AD compared to 22 controls, using single photon emission computed tomography (SPECT). We found that, compared with control subjects, Kana writing to dictation and copying Kanji words were preserved in AD patients, but writing to dictating Kanji words was impaired. We classified the errors in the Kanji dictation task into four types to investigate the correlation between rCBF and the error type, as follows: non-response errors, phonologically plausible errors, non-phonologically plausible errors, and peripheral errors. Non-response errors, which indicated difficulty with retrieving Kanji graphic images, were the most frequent. When controlled for confounding factors, the number of non-response errors negatively correlated with rCBF in the left inferior parietal lobule, the posterior middle and inferior temporal gyri, and the posterior middle frontal gyrus. Thus, the impaired recall of Kanji in early Alzheimer's disease is related to dysfunctional cortical activity, which appears to be predominant in the left frontal, parietal, and temporal regions.     

Muscarinic acetylcholine receptor status in Alzheimer’s disease assessed using (R,R) <Superscript>123</Superscript>I-QNB SPECT

Abstract Background One of the most characteristic changes in Alzheimer's disease (AD) is a deficit in cortical cholinergic neurotransmission and associated receptor changes. Objective To investigate differences in the distribution of M1/M4 receptors using (R, R) ¹²³I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in patients with mild/moderate AD and agematched controls. Also, to compare ¹²³I-QNB uptake to the corresponding changes in regional cerebral blood flow (rCBF) in the same subjects. Methods Forty two subjects (18 AD and 24 healthy elderly controls) underwent ¹²³IQNB and perfusion ^99mTc-exametazime SPECT scanning. Image analysis was performed using statistical parametric mapping (SPM99) following intensity normalisation of each image to its corresponding mean whole brain uptake. Group differences and correlations were assessed using two sample t-tests and linear regression respectively. Results Significant reductions in ¹²³I-QNB uptake were observed in regions of the frontal rectal gyrus, right parahippocampal gyrus, left hippocampus and areas of the left temporal lobe in AD compared to controls (height threshold of p ≤ 0.001 uncorrected). Such regions were also associated with marked deficits in rCBF. No significant correlations were identified between imaging data and clinical variables. Conclusion Functional impairment as measured by rCBF is more widespread than changes in M1/M4 receptor density in mild/moderate AD, where there was little or no selective loss of M1/M4 receptors in these patients that was greater than the general functional deficits shown on rCBF scans.     

Cerebral perfusion patterns in vascular dementia of Binswanger type compared with senile dementia of Alzheimer type: a SPECT study

Summary Cerebral perfusion patterns in 18 cases with vascular dementia of Binswanger type (VDBT) (8 moderate and 10 severe cases) were compared with 25 cases with senile dementia of Alzheimer type (SDAT) (16 moderate and 9 severe cases) and 14 controls by single photon emission computed tomography usingN-isopropyl-p-¹²³I iodoamphetamine (IMP) as a tracer. The cerebral: cerebellar IMP uptake ratio (%) (CCR) was used as a measure of relative cerebral perfusion. The CCRs were about 85–90% in all areas in controls. Moderate VDBT patients showed a remarkable decrease of CCRs in the basal grey region (thalamus and basal ganglia) (right 79%, left 77%) and in the frontal area (right 79%, left 80%) (P<0.01). In severe VDBT patients a significant decrease of the CCR was noted in all regions (P<0.01). The decrease of mean CCRs in the hemispheres was significantly correlated with the severity of disease determined by psychometric testing. Patients with SDAT showed a significant decrease of the CCR in the parietal (right 71%, left 74%) and right temporal (78%) areas in the moderate stage (P<0.01), and further progression of dementia was associated with low perfusion areas extending to the frontal areas (78%,P<0.01). These differences in the perfusion patterns and their changes with progression of the illnesses may be reflected in characteristic clinical features.     

Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity

Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score greater than 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS less than or equal to 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS less than 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances.     

Regional cerebral blood flow changes in a patient with delusional parasitosis before and after successful treatment with risperidone: a case report

The pathophysiology and appropriate pharmacological interventions for delusional parasitosis (DP) remain unknown. Here, we present a case of DP following brain infarction of the right temporoparietal region. Pharmacotherapy with risperidone resulted in a dramatic therapeutic response over a short period. In a sequential N-isopropyl-p-[(123)I]-iodoamphetamine single photon emission computed tomography ([(123)I]-IMP SPECT) study, post-treatment SPECT images revealed a marked increase of rCBF in the large areas including the bilateral frontal and left temporoparietal regions, the right parietal operculum and the bilateral basal ganglia, in contrast to pre-treatment SPECT images showing a global decrease of rCBF. Our clinical outcome suggests the efficacy and safety of risperidone for treatment of DP and that both dopaminergic and serotonergic dysfunction may play a role in DP. Our sequential SPECT findings suggest that psychiatric improvement of DP is associated with increased rCBF.     

Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis

BACKGROUND: Specific binding to dopamine transporters may serve as a tool to detect early loss of nigrostriatal dopaminergic neurons in patients with Parkinson's disease. OBJECTIVE: To determine striatal dopamine transporter binding using the cocaine analogue [I-123]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chl orophenyl) tropane ([I-123]IPT) and single photon emission computed tomography. PATIENTS AND METHODS: We studied 9 control subjects (mean age, 58 years; range, 41-69 years) and 28 patients with early Parkinson's disease (Hoehn and Yahr stages I [n = 14] and II [n = 14] [symptom duration, <5 years]; mean age, 55.5 years; range, 36-71 years). Single photon emission computed tomography was performed 90 minutes after injection of 120 to 150 MBq of radioactive [I-123]IPT. RESULTS: Specific striatal [I-123] IPT binding (mean +/- SD) was significantly reduced in patients with early Parkinson's disease (ipsilateral striatum: 4.09+/-0.97; range, 2.46-6.40; contralateral striatum: 3.32+/-0.76; range, 1.80-5.13) compared with controls (left striatum: 7.28+/-0.94; range, 5.78-8.81; right striatum: 7.41+/-1.28; range, 5.58-9.44). IPT binding ratios (mean +/- SD) were significantly lower in patients with Hoehn and Yahr stage II (ipsilateral striatum: 3.47+/-0.75; contralateral striatum: 2.96+/-0.73) compared with those with Hoehn and Yahr stage I (ipsilateral striatum: 4.72+/-0.75; contralateral striatum: 3.69+/-0.61) (P<.001). The ipsilateral striatum of patients with Hoehn and Yahr stage I showed a significant mean+/-SD reduction of IPT binding (ipsilateral striatum: 4.72+/-0.75) compared with either right or left striatum of controls (P<.001). Only in 1 patient was IPT binding to the ipsilateral striatum (ratio, 6.40) higher than the lowest value observed in the striatum of a control subject (ratio, 5.58). CONCLUSIONS: Use of [I-123] IPT and single photon emission computed tomography demonstrates a reduction of dopamine transporter binding in patients with early Parkinson's disease. Significantly reduced IPT binding already observed in the ipsilateral striatum of patients with Hoehn and Yahr stage I demonstrates the potential of this method to detect preclinical disease.     

Regional cerebral blood flow in catatonic schizophrenia

Single photon emission computed tomography (SPECT) with ¹²³I-iodoamphetamine (IMP) as tracer was used to study regional cerebral blood flow (rCBF) distribution in six patients with the catatonic subtype of schizophrenia (DSM-III-R). IMP-SPECT imaging revealed a significant reduction of rCBF in the parietal lobes of both hemispheres. Three-dimensional reconstruction of the SPECT images identified the superior region of the frontoparietal lobe as the most severely affected region. The pattern of rCBF deficits observed in catatonic schizophrenia differs markedly from that seen in 13 patients with other subtypes of schizophrenia and 7 normal control subjects. These observations indicate that parietal lobe dysfunction may be an important component in the pathology of the catatonic subtype of schizophrenia.     

Unaltered dopamine transporter availability in adult attention deficit hyperactivity disorder

OBJECTIVE: The authors examined whether patients with attention deficit hyperactivity disorder (ADHD) have altered striatal dopamine transporter levels, which may explain psychostimulant effects in this disorder. METHOD: Single photon emission computed tomography and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) were used to assess dopamine transporter availability in nine adult patients with ADHD (eight of whom were stimulant naive) and nine age- and gender-matched healthy comparison subjects. RESULTS: Striatal [(123)I]beta-CIT binding did not differ significantly between the ADHD and comparison subjects. CONCLUSIONS: The findings suggest that a hypothesized dysregulation of dopamine function in ADHD does not entail altered dopamine transporter levels.     

Quantitative changes in mesial temporal volume, regional cerebral blood flow, and cognition in Alzheimer's disease.

Twenty-six patients with moderately severe Alzheimer's disease (AD) and 16 normal control subjects were studied using either quantitative magnetic resonance imaging (MRI) measures of mesial temporal atrophy (15 patients with AD and 16 normal control subjects) and/or quantitative radioactive iodine 123-N-isopropyl-iodoamphetamine single-photon emission computed tomography (SPECT) assessment of regional cerebral blood flow (20 patients with AD and eight normal control subjects). Nine individuals with AD and eight normal control subjects underwent both structural and functional imaging. On MRI, patients and controls were best discriminated using left amygdala and entorhinal cortex volumes, and on SPECT they were best discriminated by relative left temporoparietal cortex blood flow. Combining these MRI and SPECT measures yielded 100% discrimination. Relative left temporoparietal SPECT regional cerebral blood flow and left superior temporal gyral MRI volume correlated best with severity of cognitive deficit in patients with AD. Mesial temporal MRI atrophy exceeded generalized cerebral shrinkage. Both SPECT and MRI regional changes accorded with areas known to be affected by AD neuropathology.     

The investigation of Alzheimer''s disease with single photon emission tomography.

Twenty patients satisfying standard clinical criteria for Alzheimer's disease (AD) and six age-matched normal controls were studied using 99mTc hexamethyl-propyleneamine oxime and single photon emission tomography. The AD patients had lower regional cerebral blood flow (rCBF) in the temporal and posterior parietal lobes compared to controls. AD patients with apraxia and aphasia had lower rCBF in the lateral temporal and posterior parietal lobes than AD patients without these features. Within the AD group, correlations were found between neuropsychological tests and rCBF: praxis correlated with posterior parietal activity, memory with left temporal lobe activity and language with activity throughout the left hemisphere.