Clinical deficits in Huntington disease correlate with reduced striatal uptake on iodine-123 epidepride single-photon emission tomography.

Huntington disease (HD) is characterized by severe abnormalities in neurotransmitter concentrations and neuroreceptor density. Quantitative changes in dopamine D(2) receptors occur in the early stages of HD and may be detectable with functional neuroimaging techniques. The aim of this study was to determine whether dopamine D(2) receptor imaging with single-photon emission tomography (SPET) identifies preclinical abnormalities in HD. The study population comprised 32 subjects from families affected by HD: 11 were genetically normal while 21 were genetically positive for HD (seven asymptomatic, six early, three moderate and five advanced findings). Disease severity was determined using a standardized quantitative neurological examination (QNE) and the mini-mental status examination (MMSE). Subjects underwent brain SPET imaging 120 min following intravenous injection of iodine-123 epidepride. Ratios of target (striatal) to nontarget (occipital or whole-brain) uptake were calculated from the reconstructed image data. Striatum to occiput and striatum to whole-brain count ratios correlated negatively with disease stage (P=0.002 and P=0.0002) and QNE (P<0. 002 and P=0.0002), and positively with the MMSE (P=0.001 and P<0. 001). Uptake was significantly reduced in the moderate-advanced subjects but was still normal for the asymptomatic and early symptomatic stages. It is concluded that reductions in striatal dopamine D(2) receptor density can be detected with (123)I epidepride at moderate or advanced stages of HD. In contrast to other reports, we could not identify abnormalities in clinically unaffected or early stages of HD.     

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D₂ receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.     

Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas

We compared pituitary iodine-123 epide- pride single-photon emission tomography (SPET) and ¹²³I-IBZM SPET for the in vivo imaging of dopamine D₂ receptors in 15 patients with clinically non-functioning pituitary adenomas. Four patients with dopamine agonist-sensitive macroprolactinomas were studied as positive controls. The uptake of radioactivity in the pituitary was established using a visual scoring system and an uptake index calculated by dividing the average count rates in the pituitary area by the average count rates in the cerebellum. All four macroprolactinomas showed specific binding of ¹²³I-epidepride, but only one showed specific binding of ¹²³I-IBZM. Specific binding of ¹²³I-epidepride was demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%), but specific binding of ¹²³I-IBZM was shown in only 6 of these 15 cases (40%). The uptake of ¹²³I-epidepride in the pituitary region was consistently higher than that of ¹²³I-IBZM. None of the patients who showed absence of uptake of ¹²³I-epidepride in the pituitary area showed uptake of ¹²³I-IBZM in this area. In conclusion: ¹²³I-epidepride SPET is superior to ¹²³I-IBZM SPET for the visualization of dopamine receptor-positive pituitary adenomas. Therefore, ¹²³I-epidepride should replace ¹²³I-IBZM for future D₂ receptor SPET studies of pituitary adenomas. ¹²³I-epidepride SPET potentially might serve to predict the response of clinically non-functioning pituitary adenomas to dopamine agonist therapy. Received 11 July and in revised form 25 September 1998     

Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography

Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer's disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [¹²³I]4-iododexetimide in five mildly affected patients with probable Alzheimer's disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [¹²³I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intea-observer variability was 3.6% and inter-observer results showed consistent differences in [¹²³I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [¹²³I]4-iododexetimide binding is reduced in patients with mild probable. Alzheimer's disease in areas of temporal and temporoparietal cortex.     

Striatal and extrastriatal imaging of dopamine D2 receptors in the living human brain with [123I]epidepride single-photon emission tomography

The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D₂ receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91±0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45–60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [¹²³I]epidepride can be used for imaging striatal and extrastriatal dopamine D₂ receptor sites in the living human brain.     

Relationship between clinical features of Parkinson's disease and presynaptic dopamine transporter binding assessed with [123I]IPT and single-photon emission tomography

IPT [N-(3-iodopropen-2-yl)-2-carbome-thoxy-3-(4-chlorophenyl) tropane] is a new cocain analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1–2 h post injection. In the present study [¹²³I]IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40–79 years) and eight age-matched controls were studied. SPET imaging was performed 90–120 min after injection of 160–185 MBq [¹²³I]IPT using a triple-head camera. For semiquantitative evaluation of specific [¹²³I]IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [¹²³I]IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [¹²³I]IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [¹²³I]IPT binding was significantly correlated with disease duration (r=–0.7,P<0.0001) but not with the age of PD patients (r=–0.10,P=0.61). Specific [¹²³I]IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. Our findings indicate that [¹²³I]IPT SPET may be a useful technique to estimate the extent of nigrostriatal degeneration in PD patients. Close relationships between striatal [¹²³I]IPT binding and clinical features of the disease suggest that this method can be used to objectively follow the course and progression of PD. The reduced putamen to caudate ratios observed even in patients with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis in the early course of PD.     

Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography

This double-blind, placebo-controlled study assessed pharmacologically induced endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in endogenous DA release after injection of the psychostimulant drug methylphenidate were evaluated by single-photon emission tomography (SPET) and constant infusion of iodine-123 iodobenzamide ([¹²³I]IBZM), a D₂ receptor radioligand that is sensitive to endogenous DA release. Methylphenidate induced displacement of striatal [¹²³I]IBZM binding, resulting in a significantly decrease in the specific to non-specific [¹²³I]IBZM uptake ratio (average: 8.6%) in comparison with placebo (average: –1.9%). Moreover, injection of methylphenidate induced significant behavioural responses on the following items: excitement, anxiety, tension, and mannerisms and posturing. The results of this study demonstrate the feasibility of using constant infusion of [¹²³I]IBZM and SPET imaging to measure endogenous DA release after methylphenidate challenge and to investigate neurochemical aspects of behaviour.     

In vivo effects of olanzapine on striatal dopamine D2/D3 receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D₂/D₃ receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [¹²³I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [¹²³I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrance of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [¹²³I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D₂/D₃ receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR–BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D₂/D₃ receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR–BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D₂/D₃ receptor availability revealed an exponential dose-response relationship (r=–0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D₂/D₃ availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D₂/D₃ striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D₂/D₃ receptor affinity and a similar 5HT₂ receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D₂/D₃ receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D₂/D₃ and 5HT₂ receptor antagonism. Received 6 March 1999 / in revised form 11 April 1999     

Automatic segmentation of dynamic neuroreceptor single-photon emission tomography images using fuzzy clustering

The segmentation of medical images is one of the most important steps in the analysis and quantification of imaging data. However, partial volume artefacts make accurate tissue boundary definition difficult, particularly for images with lower resolution commonly used in nuclear medicine. In single-photon emission tomography (SPET) neuroreceptor studies, areas of specific binding are usually delineated by manually drawing regions of interest (ROIs), a time-consuming and subjective process. This paper applies the technique of fuzzy c-means clustering (FCM) to automatically segment dynamic neuroreceptor SPET images. Fuzzy clustering was tested using a realistic, computer-generated, dynamic SPET phantom derived from segmenting an MR image of an anthropomorphic brain phantom. Also, the utility of applying FCM to real clinical data was assessed by comparison against conventional ROI analysis of iodine-123 iodobenzamide (IBZM) binding to dopamine D₂/D₃ receptors in the brains of humans. In addition, a further test of the methodology was assessed by applying FCM segmentation to [¹²³I]IDAM images (5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio] benzyl alcohol) of serotonin transporters in non-human primates. In the simulated dynamic SPET phantom, over a wide range of counts and ratios of specific binding to background, FCM correlated very strongly with the true counts (correlation coefficient r ²>0.99, P<0.0001). Similarly, FCM gave segmentation of the [¹²³I]IBZM data comparable with manual ROI analysis, with the binding ratios derived from both methods significantly correlated (r ²=0.83, P<0.0001). Fuzzy clustering is a powerful tool for the automatic, unsupervised segmentation of dynamic neuroreceptor SPET images. Where other automated techniques fail completely, and manual ROI definition would be highly subjective, FCM is capable of segmenting noisy images in a robust and repeatable manner. Received 16 November 1998 and in revised form 20 January 1999     

Potential of iodine-123 metaiodobenzylguanidine single-photon emission tomography to detect abnormal functional status of the pulmonary neuroadrenergic system in irradiated lung

The potential of iodine-123 metaiodobenzylguanidine (MIBG) to detect functional abnormalities of the pulmonary neuroadrenergic system (PNS) in irradiated lung areas (ILAS) was preliminarily explored using single-photon emission tomography (SPET). The subjects included five healthy subjects and a total of 31 patients with peripheral-type lung cancer treated by radiation; 15 patients (group A) had received a dose of less than 36 Gy (mean ± SD: 28.2 ±6.2 Gy), and 16 patients (group B) had received a higher dose (mean ± SD: 51.2 ± 3.5 Gy) at the time of examination. MIBG SPET scans aquired 15 min and 3 h after injection were used to measure the MIBG uptake ratio (count ratio of the ILA to the contralateral non-ILA) and the clearance rate [percentage of (early counts – delayed counts)/early counts] from the ILAs without noticeable abnormal opacities on chest computed tomography scan. Lung perfusion changes were also assessed by technetium-99m macroaggregated albumin SPET. By contrast to the homogeneous MIBG uptake in the lungs of the healthy subjects, MIBG uptake was folcally decreased in correspondence with the ILAs in all patients, including 11 patients (73.3%) of group A with relatively preserved lung perfusion. The reduction MIBG uptake was significant (P<0.0001), and the MIBG clearance rate from the ILAs was also significantly faster than the clearance rates from the normal lungs and contralateral non-ILAs (both P<0.01). Group B patients showed significantly lower MIBG uptake and faster clearance from the ILAs than group A patients (P<0.001 and P<0.05, respectively), although there was no significant difference in the clearance from the non-ILAs. Overall, MIBG uptake/clearance from the ILAs correlated significantly with the radiation dose in the 31 patients (r = –0.656; P<0.0001 and r = 0.387; P<0.05, respectively). Perfusion changes were inversely correlated with the clearance from the ILAs (r = –0.432, P<0.05), but did not correlate with MIBG uptake. These preliminary results suggest that MIBG may have the potential to be a marker of abnormal functional status of the PNS produced by irradiation and may facilitate investigation of irradiation lung injury independently of morphological or lung perfusion changes. Received 11 December 1998 and in revised form 10 February 1999     

A simple method for the quantification of benzodiazepine receptors using iodine-123 iomazenil and single-photon emission tomography

Iodine-123 iomazenil (Iomazenil) is a ligand for central type benzodiazepine receptors that is suitable for single-photon emission tomography (SPET). The purpose of this study was to develop a simple method for the quantification of its binding potential (BP). The method is based on a two-compartment model (K ₁, influx rate constant;k ₂, efflux rate constant;V _T (=K ₁/k ₂), the total distribution volumes relative to the total arterial tracer concentration), and requires two SPET scans and one blood sampling. For a given input function, the radioactivity ratio of the early to delayed scans can be considered to tabulate as a function ofk ₂, and a table lookup procedure provides the correspondingk ₂ value, from whichK ₁ andV _T values are then calculated. The arterial input function is obtained by calibration of the standard input function by the single blood sampling. SPET studies were performed on 14 patients with cerebrovascular diseases, dementia or brain tumours (mean age±SD, 56.0±12.2). None of the patients had any heart, renal or liver disease. A dynamic SPET scan was performed following intravenous bolus injection of Iomazenil. A static SPET scan was performed at 180 min after injection. Frequent blood sampling from the brachial artery was performed on all subjects for determination of the arterial input function. Two-compartment model analysis was validated for calculation of theV _T value of Iomazenil. Good correlations were observed betweenV _T values calculated by three-compartment model analysis and those calculated by the present method, in which the scan time combinations (early scan/delayed scan) used were 15/180 min, 30/180 min or 45/180 min (all combinations:r=0.92), supporting the validity of this method. The present method is simple and applicable for clinical use.     

Dementia with Lewy bodies: a study of post-synaptic dopaminergic receptors with iodine-123 iodobenzamide single-photon mission tomography

Dementia with Lewy bodies (DLB) can at present only be diagnosed with certainty by neuropathological examination. Diagnosis during life remains at best probable, based on the presence of symptoms known from autopsy studies to be frequently associated with DLB. The greatest practical clinical problem lies in distinguishing DLB arid Alzheimer's disease (AD). In DLB there is a considerable degeneration of nigral neurones with depletion of striatal dopamine. In contrast, AD is not associated with significant changes in dopamine metabolism. Iodine-123 iodobenzamide single-photon emission tomography (IBZM-SPET) measures post-synaptic dopamine D₂ neuroreceptor availability in the corpus striatum, but is nevertheless a method for assessing the integrity of the nigrostriatal dopaminergic pathway. Sixteen clinically diagnosed DLB patients, 15 normal controls arid 13 AD patients underwent IBZM-SPET. All subjects were scanned 1.5–2 h after intravenous injection of 185 MBq of¹²³I-IBZM. Circular regions of iriterest were employed to calculate radioactivity ratios in each hemisphere as follows: caudate nucleus/frontal cortex, putamen/frontal cortex arid caudate nucleus/putamen. The DLB patients had significantly lower left caudate/putamen ratios (95% confidence intervals: DLB 0.893–0.965, AD 0.972–1.175, controls 1.031–1.168) than either controls or AD patients, and significantly lower right caudate/putamen ratios (95% confidence intervals: DLB 0.926–1.019, AD 0.954–1.103, controls 1.027–1.144) chan controls. Our data suggest that patients with DLB diagnosed by clinical criteria have changes in striatal post-synaptic D₂ receptors. This may be of value in distinguishing DLB from AD during life.     

Differential distribution of striatal [123I]β-CIT in Parkinson’s disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([¹²³I]β-CIT) is important for the assessment of disease severity and progression in patients with Parkinson’s disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [¹²³I]β-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24±2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3′′). ANOVA revealed a global reduction of V3′′ in all ROIs of PD and PSP patients compared with normal controls (P<0.0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3′′ caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [¹²³I]β-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP. Received 1 February and in revised form 7 May 1998     

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D₂ receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [¹²³I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D₂ receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=–0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D₂ receptors with SPET using [¹²³I]epidepride. Received 6 September and in revised form 21 October 1999     

Delayed cerebral radionecrosis with a high uptake of 11C-methionine on positron emission tomography and 201Tl-chloride on single-photon emission computed tomography

A 47-year-old woman, who 2.5 years previously had undergone resection of a malignant astrocytoma of the left temporal lobe followed by radiotherapy, was found to have a mass in the left frontal lobe. This showed high uptake of thallium-201 (²⁰¹Tl) on single-photon emission computed tomography and ¹¹C-methionine on positron-emission tomography, suggesting recurrent tumour. Histological examination of the resected lesion, however, revealed it to be radionecrosis. This case thus illustrates a diagnostic pitfall in the use of these investigations for distinguishing radionecrosis from recurrent malignant glioma. Received: 19 September 1997 Accepted: 16 October 1997     

In vivo imaging of GABAA receptors using sequential whole-volume iodine-123 iomazenil single-photon emission tomography

Using a brain-dedicated triple-headed single-photon emission tomography (SPET) system, a sequential whole-volume imaging protocol has been devised to evaluate the regional distribution of iodine-123 iomazenil binding to GABA_A receptors in the entire brain. The protocol was piloted in eight normal volunteers (seven males and one female; mean age, 24.8±3.9 years). The patterns obtained were largely compatible with the known distribution of GABA_A receptors in the brain as reported in autoradiographic studies, with cerebral cortical regions, particularly the occipital and frontal cortices, displaying the highest¹²³I-iomazenil uptake. Measures of time to peak uptake and tracer washout rates presented with the same pattern of regional variation, with later times to peak and slower washout rates in cortical regions compared to other brain areas. Semiquantitative analysis of the data using white matter/ventricle regions as reference demonstrated a plateau of specific¹²³I-iomazenil binding in neocortical and cerebellar regions from 60–75 min onwards. These data demonstrate the feasibility of sequential, dynamic whole-volume¹²³I-iomazenil SPET imaging. The protocol may be particularly useful in the investigation of neuropsychiatric conditions which are likely to involve more than one focus of GABA abnormalities, such as anxiety disorders and schizophrenia.     

Artificial neural networks that use single-photon emission tomography to identify patients with probable Alzheimer's disease

Single-photon emission tomographic (SPET) images using technetium-99m labelled hexamethylpropylene amine oxime were obtained from 97 patients diagnosed as having Alzheimer's disease, as well as from a comparison group of 64 normal subjects. Multiple linear regression was used to predict subject type (Alzheimer's vs comparison) using scintillation counts from 14 different brain regions as predictors. These results were disappointing: the regression equation accounted for only 33.5% of the variance between subjects. However, the same data were also used to train parallel distributed processing (PDP) networks of different sizes to classify subjects. In general, the PDP networks accounted for substantially more (up to 95%) of the variance in the data, and in many instances were able to distinguish perfectly between the two subjects. These results suggest two conclusions. First, SPET images do provide sufficient information to distinguish patients with Alzheimer's disease from a normal comparison group. Second, to access this diagnostic information, it appears that one must take advantage of the ability of PDP networks to detect higher-order nonlinear relationships among the predictor variables.     

Redistribution in I-123 N-isopropyl-p iodoamphetamine single-photon emission computed tomography in cerebrovascular disease and the effects of rehabilitation

We performed N-isopropyl-p (I-123) iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) on 28 patients with severe cerebrovascular disease before rehabilitation, and compared the degree of redistribution and the assessment of activities of daily living (ADL). We calculated a redistribution (RD) ratio in the central and peripheral parts of the lesions: RD ratio (c) and RD ratio (p). We classified the patients into four groups based on the degree of redistribution: complete: both RD ratio (c) and (p) > or = 75; peripheral: RD ratio (c) < 75, RD ratio (p) > or = 75; incomplete: both RD ratio (c) and (p) < 75 and at least one of RD ratio (c) or (p) > or = 25; no redistribution: both RD ratio (c) and (p) < 25. We assessed the ADL using the modified Barthel index (BI). deltaBI was defined as BI after rehabilitation-BI before rehabilitation (BIpost-BIpre). The deltaBI of the four groups were as follows: complete-redistribution group (40.8 +/- 22.8), peripheral-redistribution group (40.0 +/- 15.8), incomplete-redistribution group (27.2 +/- 22.6), no-redistribution group (8.8 +/- 12.3). The deltaBI of the complete and peripheral redistribution groups were significantly higher than that of the no-redistribution group. However, deltaBI was almost the same in the complete- and peripheral-redistribution groups. This suggests that the effect of rehabilitation might be closely related to the viability of the peripheral part of the lesion.     

Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine single-photon emission tomography in patients with Joseph disease

Regional cerebral blood flow (rCBF) was measured in five Japanese patients who were clinically diagnosed as having Joseph disease, also called Machado-Joseph disease or Azorean disease, using N-isopropyl p-[¹²³I]iodoamphetamine (IMP) and single-photon emission tomography (SPET). Cerebellar atrophy was evaluated by a five-step rating scale as defined on X-ray computed tomography (X-CT). Compared with ten age-matched normal controls (mean cerebellar CBF ± SD: 66.9 ± 6.6 ml/100 g/min), rCBF in patients with Joseph disease was significantly decreased in the cerebellum (mean ± SD: 50.2 ± 7.3 m1/100 g/min). No significant relationship, however, was found between the decrease in rCBF in the cerebellum and the degree of cerebellar atrophy on X-CT. rCBF in the cerebellum was minimally decreased in one patient who had severe cerebellar atrophy and in two patients with moderate atrophy. These data may support the findings that Purkinje cells in the cerebellum are almost normal in Joseph disease, and that the granular and molecular layers remain intact in spite of cortical atrophy of the cerebellum. It is concluded that [¹²³I]-IMP SPET is able to identify pathological and metabolic changes in the cerebellum that do not appear on X-CT or magnetic resonance imaging, and thus is useful for the diagnosis of Joseph disease. Correspondence to: N. Takahashi     

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2.3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction. Received 3 August and in revised form 1 October 1997