eZIS Analysis Research Articles

Specifically Regional Cerebral Hypoperfusion in a Case of Highly Suspected Sporadic Creutzfeldt-Jakob Disease on 99mTc-ECD SPECT/CT with Easy Z-Score Imaging System Analysis.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly-progressive dementing illness, the challenge of diagnosis during life. We presented a 78-year-old woman reported stupor, right facial palsy, and fluctuations in consciousness. 99mTc-ECD brain SPECT/CT with eZIS analysis revealed significant decreased regional cerebral blood flow mainly in specific regions of Alzheimer’s disease as the published article reported with involving frontal region. Brain DWI MRI increased signal intensities corresponding to similar location of 99mTc-ECD brain SPECT/CT. In this case, we reported the pattern of decreased rCBF may correlate to rapidly progressive dementia and associated neurodegenerative symptoms of the highly suspected sCJD patient.

Neuropsychological and regional cerebral blood flow of posterior parietal area features in patients with Parkinson's disease with mild cognitive impairment

This study aimed to clarify associations between neuropsychological scales and regional cerebral blood flow (rCBF) of on ‍123I-IMP-SPECT in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). Forty-two participants (mean age, 65.5 ± 8.9 years; mean disease duration, 11.1 ±5.7 years) were evaluated using the Wechsler Adult Intelligence Scale, third edition (WAIS-III), Wechsler Memory Scale, revised (WMS-R), Stroop test, Category word fluency, Auditory verbal learning test, Raven colored progressive matrices, Trail Making Test-B, and Clock drawing test. Participants were classified into PD-MCI and PD non-demented (PD-ND) using ten of these scales or its subtests. The rCBF of the posterior cingulate gyrus, precuneus, and parietal lobes was evaluated by ‍123I-IMP-SPECT using the easy Z-‍score imaging system (eZIS analysis). Extent was the extent index of voxels showing z-score > 2, and Severity was mean z-score in those regions on eZIS analysis. Cingulate island sign score (CIScore) was the ratio of integrated z-scores of the posterior cingulate gyrus to those of the posterior cortex.Twenty-three participants were diagnosed with PD-MCI (55%). The rCBF indices were significantly increased in the PD-MCI group compared to the PD-ND group (Extent: P = 0.047; CIScore: P = 0.006). These indices were significantly correlated with WAIS-III Processing Speed (Extent: P = 0.041, R = -0.317; Severity: P = 0.047, R = -0.309), Stroop effect (Extent: P = 0.003, R = 0.443; Severity: P = 0.004, R = 0.437), WMS-R Visual memory (Extent: P = 0.019, R = -0.361; Severity: P = 0.014, R = -0.375), and Delayed memory score (Extent: P = 0.005, R = -0.423; Severity: P = 0.044, R = -0.312). The rCBF indices showed no correlations with the number of impaired cognitive domains. Collectively, decreased posterior parietal area rCBF and lower scores on selective neuropsychological scales might be helpful to detect a transition period from PD-MCI to PD-D.

Decreased midbrain cerebral blood flow determined by an easy Z score imaging system (eZIS) analysis of 123I-IMP in patients with progressive supranuclear palsy (PSP)

Decreased midbrain cerebral blood flow determined by an easy Z score imaging system (eZIS) analysis of 123I-IMP in patients with progressive supranuclear palsy (PSP)

The evaluation of brain perfusion SPECT using an easy Z-score imaging system in the mild cognitive impairment subjects with brain amyloid-β deposition

ObjectiveThe analysis of 99mTc-ECD single-photon emission computed tomography (SPECT) images using the easy Z-score imaging system (eZIS) program is useful for the diagnosis of early AD in daily medical practice. However, it remains unclear whether eZIS analysis can identify the amnestic mild cognitive impairment (MCI) subjects with brain amyloid-β deposition. The aim of this study was to evaluate the usefulness of an eZIS analysis for predicting amnestic MCI subjects with brain amyloid β deposition. Patients and methodsTwenty-three subjects with MCI (10 men and 13 women, mean age; 74.2 years) underwent brain perfusion SPECT and 11C-Pittsburgh Compound B positron emission tomography (PiB-PET). MCI subjects were divided into PiB-positive and PiB-negative subgroups. SPECT data was analyzed using the Specific Volume of interest Analysis of the eZIS program. Three indicators (severity, extent, and ratio) were calculated automatically and compared between the two subgroups. ResultsFive of 12 (41.7%) subjects in the PiB-positive subgroup and three of 11 (27.3%) subjects in the PiB-negative subgroup showed the abnormal value for each indicator. The frequency of subjects with abnormal ratio values was significantly higher in the PiB-positive subgroup compared to the PiB-negative subgroup (p=0.02), whereas that of subjects with abnormal values in severity and extent did not differ among the two subgroups. In particular, all subjects in the PiB-negative subgroup showed normal ratio values. Moreover, the subjects with abnormal values on two indicators, including ratio, or on all three indicators, showed PiB-positive. ConclusionThe analysis of brain perfusion SPECT using an eZIS program cannot identify the amnestic MCI subjects with brain amyloid-β deposition. However, abnormal three indicators or normal ratio values may be helpful SPECT findings for predicting the results of PiB-PET in the amnestic MCI subjects.

Decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata determined by an easy Z-score (eZIS) analysis of 99mTc-ECD-SPECT images in a case of MM2-thalamic-type sporadic Creutzfeldt–Jakob disease

We report a case of autopsy-verified MM2-thalamic-type sporadic Creutzfeldt–Jakob disease (sCJD) in a 46-year-old patient with a 16-month history of abnormal behavior, progressive dementia, insomnia, and speech disturbances without family history. Neurological examination revealed progressive dementia, frontal signs, insomnia, speech disturbance, gait disturbance and bilaterally exaggerated tendon reflexes. Both brain MRI and cerebrospinal fluid examinations, including 14-3-3 protein, yielded normal results. An easy Z-score (eZIS) analysis for 99mTc-ethyl cysteinate dimer-single photon emission computed tomography (99mTc-ECD-SPECT) revealed decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata. PRNP gene analysis revealed methionine homozygosity at codon 129 without mutation. Neuropathological examinations revealed severe neuronal loss, gliosis, and hypertrophic astrocytosis in the medial thalamus and inferior olivary nucleus. A slight depletion of Purkinje cells was observed. PrP immunostaining showed no obvious PrP deposits in the basal ganglia, thalamus, cerebellum, or brainstem; however, mild synaptic-type PrP deposits with some smaller plaque-like structures were only partially observed in the localized region of the frontal lobe with the spongiform change.Western blot analyses of protease-resistant PrP showed a type 2 pattern. In conclusion, eZIS analysis of 99mTc-ECD-SPECT images is useful for detecting both thalamic and medullary lesions. This is the first case of medullary lesions detected in a live patient with MM2-thalamic-type sCJD using SPECT.

Evaluation of the difference-correction effect of the gamma camera systems used by easy Z-score Imaging System (eZIS) analysis

Objective We examined the difference of the effect by data to revise a gamma camera difference. The difference-correction method of the camera is incorporated in eZIS analysis.MethodsWe acquired single photon emission computed tomography (SPECT) data from the three-dimensional (3D) Hoffman brain phantom (Hoffman), the three-dimensional brain phantom (3D-Brain), Pool phantom (pool) and from normal subjects (Normal-SPECT) to investigate compensating for a difference in gamma camera systems. We compared SPECT counts of standard camera with the SPECT counts that revised the difference of the gamma camera system (camera). Furthermore, we compared the “Z-score map (Z-score)”. To verify the effect of the compensation, we examined digitally simulated data designed to represent a patient with Alzheimer’s dementia. We carried out both eZIS analysis and “Specific Volume of interest Analysis (SVA)”.ResultsThere was no great difference between the correction effect using Hoffman phantom data and that using 3D-Brain phantom data. Furthermore, a good compensation effect was obtained only over a limited area. The compensation based on the pool was found to be less satisfactory than any of the other compensations according to all results of the measurements examined in the study. The compensation based on the Normal-SPECT data resulted in a Z-score map (Z-score) for the result that approximated that from the standard camera. Therefore, we concluded that the effect of the compensation based on Normal-SPECT data was the best of the four methods tested.ConclusionsBased on eZIS analysis, the compensation using the pool data was inferior to the compensations using the other methods tested. Based on the results of the SAV analysis, the effect of the compensation using the Hoffman data was better than the effect of the compensation using the 3D-Brain data. By all end-point measures, the compensation based on the Normal-SPECT data was more accurate than the compensation based on any of the other three phantoms.

Pitfalls of voxel-based amyloid PET analyses for diagnosis of Alzheimer's disease: artifacts due to non-specific uptake in the white matter and the skull.

Two methods are commonly used in brain image voxel-based analyses widely used for dementia work-ups: 3-dimensional stereotactic surface projections (3D-SSP) and statistical parametric mapping (SPM). The methods calculate the Z-scores of the cortical voxels that represent the significance of differences compared to a database of brain images with normal findings, and visualize them as surface brain maps. The methods are considered useful in amyloid positron emission tomography (PET) analyses to detect small amounts of amyloid-β deposits in early-stage Alzheimer's disease (AD), but are not fully validated. We analyzed the (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) amyloid PET imaging of 56 subjects (20 individuals with mild cognitive impairment [MCI], 19 AD patients, and 17 non-demented [ND] volunteers) with 3D-SSP and the easy Z-score imaging system (eZIS) that is an SPM-based method. To clarify these methods' limitations, we visually compared Z-score maps output from the two methods and investigated the causes of discrepancies between them. Discrepancies were found in 27 subjects (9 MCI, 13 AD, and 5 ND). Relatively high white matter uptake was considered to cause higher Z-scores on 3D-SSP in 4 subjects (1 MCI and 3 ND). Meanwhile, in 17 subjects (6 MCI, 9 AD, and 2 ND), Z-score overestimation on eZIS corresponded with high skull uptake and disappeared after removing the skull uptake ("scalping"). Our results suggest that non-specific uptakes in the white matter and skull account for errors in voxel-based amyloid PET analyses. Thus, diagnoses based on 3D-SSP data require checking white matter uptake, and "scalping" is recommended before eZIS analysis.

Brain perfusion SPECT in limbic encephalitis associated with autoantibody against the glutamate receptor epsilon 2

The aim of this study was to elucidate the single-photon emission computed tomography (SPECT) pattern at the acute stage of disease in non-herpetic limbic encephalitis (NHLE) patients associated with the N-methyl-D-aspartate-type glutamate receptor epsilon 2 (GluR ϵ2) autoantibody using Z-score imaging system (eZIS) analyses. Brain magnetic resonance imaging (MRI) and brain perfusion SPECT using technetium-99 ethyl cysteinate dimer ((99m)Tc-ECD) were performed in eight patients with NHLE (5 men and 3 women; mean age 48.8±22 years) within 20days after clinical onset. All patients had various clinical limbic-associated symptoms and no evidence of herpes simplex infection or systemic malignancies. Two of eight patients showed abnormally hyperintense lesions on diffusion-weighted images and significant hyperperfusion in ipsilateral cerebral cortex on eZIS analysis, whereas other patients showed normal MRI findings and significant hypoperfusion in one or both sides of the limbic and paralimbic areas. We suggest that (99m)Tc-ECD SPECT study using eZIS analyses may be helpful to detect the neuronal dysfunction, particularly in NHLE patients without abnormal MRI findings.

前庭神経炎急性期におけるSPECTを用いた脳血流の解析

We examined the cerebral blood flow in 6 patients with acute stage vestibular neuritis using single photon emission computed tomography (SPECT). SPECT images of cerebral blood flow were analyzed using an easy Z-score imaging system (eZIS), a method for statistical image analysis. The analysis results showed cerebral blood flow to be increased in the parieto-insular vestibular cortex (PIVC) contralateral to the affected side, whereas blood flow was decreased bilaterally in the visual cortex and Brodmann area 40 (BA40). These results were identical to those obtained in patients with acute stage vestibular neuritis using PET by Bense et al. However, in our present analysis, increased cerebral blood flow was occasionally not detected in PIVC, rendering some cases unevaluable. Blood flow lowering in BA40 tended to be predominantly left hemispheric, regardless of the diseased side. Although SPECT is considered to be inferior to PET in spatial resolution and quantifiability, we found that cerebral blood flow in patients with acute stage vestibular neuritis can be sufficiently evaluated using eZIS analysis.

Regional Cerebral Blood Flow Patterns Detected by SPECT With Easy Z-score Imaging System Analysis in Early-stage Alzheimer's Disease

The objective of this study is to investigate the characteristic patterns of regional cerebral blood flow reduction in early Alzheimer's disease (AD). Twenty patients were recruited in this study. We performed MRI(Siemens, MAGNETOM Harmony 1.0T,) and single-photon emission computed tomography (SPECT) technetium-99m cysteinate dimmer (99m Tc-ECD) (Toshiba, 7200A−DI), simultaneously, and corrected using voxel-based morphometry as to reduce the atrophic influence. We evaluated regional cerebral blood flow patterns using easy Z-score imaging system (eZIS) analysis, and we calculated the extent of each regions using voxel-based Stereotactic Extraction Estimation (vb SEE)(Level 3 classification). In 8 subjects, MRI and SPECT were reevaluated one or two years after and the comparative study was performed. There was prominent decrease in the bilateral posterior cingulated gyrus, parietal cortex, temporal cortex, and frontal cortex. The eZIS analysis with vb SEE is useful in highlighting the changes in the hypoperfusional regions. These results were in agreement with those of 3D-SSP study with SEE analysis.

Differentiation of Early-Stage Alzheimer’s Disease from Other Types of Dementia Using Brain Perfusion Single Photon Emission Computed Tomography with Easy Z-Score Imaging System Analysis

Introduction: We performed brain perfusion single photon emission computed tomography (SPECT) to evaluate computer-assisted automated discrimination of early Alzheimer’s disease (AD) from other types of dementia using the easy Z-score imaging system (eZIS). Subjects and Methods: eZIS analysis of brain perfusion SPECT images was used in patients with early AD, vascular dementia (VD), mixed dementia (VD + AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and normal controls. Significant changes in regional cerebral blood flow (rCBF) in the volume of interest were assessed in the posterior cingulate gyrus, precuneus and parietal cortices; the severity and extent of decreases in rCBF and the ratio of the extent of the decrease in rCBF to the decrease in whole-brain blood flow (rCBF ratio) were determined. Results: The severity of the decrease in rCBF in AD patients was significantly greater than in VD and FTD patients and controls. The extent of the decrease in rCBF in AD patients was significantly greater than in FTD patients and controls. The rCBF ratio in AD patients was higher than in VD and FTD patients and controls. Conclusion: The eZIS indices, especially the rCBF ratio, may be useful in establishing the differential diagnosis between early-stage AD and FTD or VD, but the differentiation of AD from VD + AD or DLB remains difficult.

統計学的脳機能画像解析における平滑化処理が解析結果に及ぼす影響

Spatial smoothing performed after spatial normalization on the easy Z-score Imaging System (eZIS) is considered to affect signal size. The purpose of this study was to analyze quantitatively the influence of the smoothing process on eZIS using the voxel of interest (VOI) method. A normal database (NDB) was established using (99m)Tc-Hexamethylpropyleneamine oxime (HMPAO) brain perfusion SPECT images of thirty healthy volunteers. Then the NDB was smoothed with various Gaussian kernels (2, 4, 8, 12, 16 mm). Artificial lesions with known volumes and reduction of tracer uptake were made on one of the healthy volunteer images, and eZIS analysis was performed on the NDB of the same Gaussian kernel, respectively. The signal size of small-sized lesions was expanded 5.1 times to the true signal size of a 12 mm Gaussian kernel. On the other hand, the medium lesion size, which was approximately the same size as the posterior cingulate gyrus, was expanded 2.9 times to true signal size. Estimation of the false positive area using the extraction estimation method at lesion size medium indicated the lowest value at 8, 12 mm Gaussian kernel smoothing. The smoothing procedure at 8-12 mm Gaussian kernel is effective to detect a focal abnormality in the brain SPECT of Alzheimer's disease.

Evaluation of brain perfusion SPECT using an easy Z-score imaging system (eZIS) as an adjunct to early-diagnosis of neurodegenerative diseases

The eZIS allows computer-assisted statistical analysis of brain perfusion SPECT images. We evaluated the diagnostic value of brain perfusion SPECT using eZIS in patients with various neurodegenerative diseases at a very early stage, within one year from onset. Methods SPECT using eZIS was performed for patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD,), idiopathic Parkinson disease (PD) and vascular Parkinsonism (VP), multiple systemic atrophy of the cerebellar type (MSA-C), cortical cerebellar atrophy (CCA) and amyotrophic lateral sclerosis (ALS). Results Decreased rCBF was observed in the posterior cingulate cortex, precuneus and parietal cortex in AD; in the frontal gyrus and insula in FTD; in the occipital lobe, precuneus gyrus and posterior cingulate cortex in DLB; in the striatum and the thalamus in VP; in the cerebellum in CCA; in the cerebellum and pons in MSA-C and in the frontal cortex including the central sulcus in ALS. Increased rCBF in the striatum, thalamus and cerebellar dentate nuclei were observed in PD. Conclusions A specific rCBF pattern was observed for each disease using eZIS analysis, consistent with previous reports. Our results showed eZIS can be easily used as an adjunct to early-diagnosis of neurodegenerative diseases in any hospital.