Development of software for measuring brain amyloid accumulation using 18 F-florbetapir PET and calculating global Centiloid scale and regional Z-score values.

BACKGROUND AND PURPOSE: Quantitative measures have been proposed to aid the visual interpretation of amyloid PET. Our objective was to develop and validate quantitative software that enables calculation of the Centiloid (CL) scale and Z-score for amyloid PET with 18 F-florbetapir. METHODS: This software was developed as a toolbox in statistical parametric mapping 12 running on MATLAB Runtime. For each participant's amyloid PET, this software calculates the CL scale using the standard MRI-guided pipeline proposed by the Global Alzheimer's Association Interactive Network (GAAIN) and generates a Z-score map for comparison with a new amyloid-negative database constructed from 20 healthy controls. In 23 cognitively impaired patients with suspected Alzheimer's disease, Z-score values for a target cortical area from the new database were compared with those from the GAAIN database constructed from 13 healthy controls. The CL values obtained using low-dose CT of PET/CT equipment were then compared with those obtained using MRI. RESULTS: The CL calculation was validated with the 18 F-florbetapir dataset in the GAAIN repository. Z-score values obtained from the new database were significantly higher (mean ± standard deviation, 1.05 ± 0.77; p < .0001) than those obtained from the GAAIN database. The use of low-dose CT provided CL scales that were highly correlated with those obtained with MRI (R2  = .992) but showed a slight yet significant underestimation (-2.1 ± 4.2; p = .013). CONCLUSIONS: Our quantification software provides the CL scale and Z-score for measuring overall and local amyloid accumulation with the use of MRI or low-dose CT.

Evaluation of lung perfusion by using lung perfusion SPECT and lung CT with breathing synchronization software.

BACKGROUND: Lung perfusion using 99mTc-macroaggregated albumin single-photon emission computed tomography (SPECT) and lung computed tomography (CT) is a useful modality for identifying patients with pulmonary artery embolism. However, conformity between SPECT and CT at the bottom of the lung is generally low. This study aims to investigate the progression of conformity between lung perfusion SPECT and lung CT using a breathing synchronization software. METHODS: Among 95 consecutive patients who underwent lung perfusion SPECT and lung CT within 14 days because of suspected pulmonary embolism between June 2019 and August 2020 in department of cardiovascular medicine, we identified 28 patients (73 ± 10 years) who had normal pulmonary artery on contrast lung CT. We compared lung volumes calculated using lung perfusion SPECT and lung CT as gold standard. Visual conformity between lung SPECT and lung CT was scored 0-4 (0: 0-25%, 1: 25-50%, 2: 50-75%, 3: 75-90%, 4: > 90%) by two specialists in nuclear medicine and assessed. RESULTS: The lung volume calculated from lung CT was 3749 ± 788 ml. The lung volume calculated from lung perfusion SPECT without using the breathing synchronization software was 3091 ± 610 ml. There was a significant difference between the lung volume calculated from CT and SPECT without using the breathing synchronization software (P < 0.01). The lung volume calculated from lung perfusion SPECT using the breathing synchronization software was 3435 ± 686 ml, and there was no significant difference between the lung volume calculated from CT and SPECT using the breathing synchronization software. The visual score improved with the use of breathing synchronization software (without software; 1.9 ± 0.6 vs. with software; 3.4 ± 0.7, P < 0.001). CONCLUSION: This study demonstrated that the breathing synchronization software could improve conformity between lung perfusion SPECT and lung CT.

Cerebral perfusion changes in chronic dizziness: A single-photon emission computed tomography study.

BACKGROUND AND PURPOSE: Dizziness may persist even after the causative vestibular imbalance subsides. Although the precise mechanism of chronic dizziness is unknown, various cerebral activity changes associated with it have been reported. To understand its mechanism in the absence of the causative vestibular imbalance, we compared cerebral changes in chronic dizziness with and without persistent vestibular imbalance. METHODS: Between September 2014 and March 2020, we examined regional cerebral blood flow (rCBF) in 12 patients having chronic post-lateral medullary infarction dizziness with persistent brainstem vestibular imbalance and 23 patients having chronic dizziness without currently active vestibular imbalance using single-photon emission computed tomography (SPECT) with 99m Technetium-ethyl cysteinate dimer. Further, we analyzed the SPECT images using a voxel-based group comparison. RESULTS: We observed a decreased rCBF in the occipital lobe and increased rCBF in the medial and inferior parts of the temporal lobe in patients having chronic dizziness with and without active vestibular imbalance compared to healthy controls. However, only patients having chronic dizziness without active vestibular imbalance exhibited increased rCBF in the frontal lobe, including the orbitofrontal cortex. CONCLUSION: This is the first study to highlight the difference in rCBF changes between patients having chronic dizziness with and without active vestibular imbalance. Decreased occipital lobe activity and increased medial and inferior temporal lobe activity may be related to keeping dizziness perception triggered regardless of the presence or absence of active vestibular imbalance, whereas increased frontal lobe activity may explain the dizziness background to persist after the disappearance of vestibular imbalance.

Characterization of human dermal sheath cells reveals CD36-expressing perivascular cells associated with capillary blood vessel formation in hair follicles.

Dermal sheath (DS) is located at the outermost border of hair follicles, comprising the connective tissue sheath of these follicles; DS cells are known to contribute to hair cycling and follicle neogenesis. However, the mechanisms by which DS cells contribute to hair formation are currently unclear. We investigated the global transcriptional profile of human DS cells in early passaged culture, compared with those of human dermal papilla cells (DP cells) and dermal fibroblasts. Vascular related genes were highly expressed in DS cells, and expression of the multi-ligand receptor, CD36, was significantly higher in DS cells than in DP cells. Further analyses with whole-mount imaging technique showed that dense networks of blood capillaries were formed in the DS of human anagen hair follicles, whereas regression of blood capillaries was observed in telogen and catagen hair follicles. We found that CD36-expressing cells were present in populations of DS cells, but were rarely observed in populations of DP cells and fibroblasts. Furthermore, our results indicated that CD36-expressing DS cells may participate in angiogenesis. Therefore, we concluded that CD36-expressing DS cells may modulate blood capillaries in hair follicles, in association with hair cycling.

Wnt activator CHIR99021-stimulated human dermal papilla spheroids contribute to hair follicle formation and production of reconstituted follicle-enriched human skin.

The aim of the present study was to accomplish de novo generation of reconstituted human skin with enriched hair follicles. Dermal papillae (DP) are known to play a crucial organizing role in hair follicle induction. However, generation of enriched human hair follicles using cultured DP cells has not been accomplished because DP cells easily lose their hair-inducing ability with culturing. To enhance the hair-inducing ability of DP cells, Wnt signaling pathway activation or three-dimensional (3D) spheroid culture methods were employed in previous studies. Herein, we assessed effects of the canonical Wnt/ß-catenin signaling activator CHIR99021 and found that it enhanced the expression of DP signature genes associated with hair-inducing ability. Further comparison of three different 3D culture methods revealed the highest expression of DP signature genes in spheroids generated by a floating drop method compared with other methods. CHIR99021 synergistically increased expression of DP signature genes in combination with floating drop culture. "Reconstituted skin assay" prepared using the most promising CHIR99021-stimulated 3D spheroids showed enrichment for human hair follicles. Labeled DP spheroids and derived cells were primarily found to be DP and dermal sheath cup (DSC) cells, implying organization of hair formation by DP spheroids. Finally, to evaluate the functional features of generated human skin and hair follicles, we injected human DSC cells, which reportedly show DP precursor behavior, and exhibit hair-inducing ability through incorporation into hair follicles, into mice. Histological studies revealed injected DSC cells in dermal sheath of hair follicles, consistent with a previous report, thus verifying the functionality of generated skin and hair follicles. Collectively, our findings demonstrate that DP spheroids synergistically stimulated by CHIR99021 and 3D culture contributed to hair follicle formation, thus making it possible to generate reconstituted hair follicle-enriched human skin with functional features.

Pattern of FDG and MET Distribution in High- and Low-Grade Gliomas on PET Images.

PURPOSE OF THE REPORT: This study aimed to determine the most effective metabolic index of FDG-PET and MET-PET to differentiate high- and low-grade gliomas, and then to characterize tumor metabolism according to the 2016 WHO classification. We also developed a new calculation method of potential infiltrative tumor volume to overcome the current limitations of tumor evaluation according to metabolic index, which focuses solely on tumor core area. MATERIALS AND METHODS: Patients who underwent both FDG-PET and MET-PET, as well as surgical treatment, were retrospectively identified. All tumors were diagnosed histologically and included 44 high-grade and 19 low-grade gliomas. Metabolic indices of tumor-to-normal (T/N) ratio and maximum value within the tumor itself were compared between high- and low-grade tumors. A calculation method for potential infiltrative tumor volume was developed and compared between these 2 grades. RESULTS: T/N, calculated as tumor value divided by normal cortex value, was the most effective (area under the curve, 0.800 for FDG-PET; area under the curve, 0.773 for MET-PET) for differentiating high- and low-grade gliomas. Potential infiltrative volume effectively distinguished between high- and low-grade glioma (43.8 ± 30.2 mL vs 14.0 ± 12.6 mL; P = 0.005 [t test]). A combination of T/N, with a cutoff value of 0.9 or higher on FDG-PET and/or 3.0 or higher on MET-PET, and potential infiltrative volume, with a cutoff value of 20.0 mL or higher, provided a diagnostic accuracy of 89% in distinguishing high- from low-grade gliomas. CONCLUSIONS: Evaluation of potential infiltrative volume surrounding the tumor core area, in addition to the T/N ratio of the tumor core, may help distinguish between high- and low-grade gliomas.

Marked Changes in Lamellar Granule and Trans-Golgi Network Structure Occur during Epidermal Keratinocyte Differentiation.

Epidermal lamellar granules transport various lipids, proteins, and protein inhibitors from the trans-Golgi network to the extracellular space, and play an important role in skin barrier formation. We elucidated the 3-dimensional structure of lamellar granules and the trans-Golgi network in normal human skin by focused ion beam scanning electron microscopy. Reconstructed focused ion beam scanning electron microscopy 3-dimensional images revealed that the overall lamellar granule structure changed from vesicular to reticular within the second layer of the stratum granulosum. Furthermore, the trans-Golgi network was well developed within this layer and spread through the cytoplasm with branched, tubular structures that connected to lamellar granules. Our study reveals the unique overall 3-dimensional structure of lamellar granules and the trans-Golgi network within the cells of the epidermis, and provides the basis for an understanding of the skin barrier formation.

Gene Expression Profiling of the Intact Dermal Sheath Cup of Human Hair Follicles.

Cells that constitute the dermal papillae of hair follicles might be derived from the dermal sheath, the peribulbar component of which is the dermal sheath cup. The dermal sheath cup is thought to include the progenitor cells of the dermal papillae and possesses hair inductive potential; however, it has not yet been well characterized. This study investigated the gene expression profile of the intact dermal sheath cup, and identified dermal sheath cup signature genes, including extracellular matrix components and bone morphogenetic protein-binding molecules, as well as transforming frowth factor beta 1 as an upstream regulator. Among these, gremilin-2, a member of the bone morphogenetic protein antagonists, was found by in situ hybridization to be highly specific to the dermal sheath cup, implying that gremlin-2 is a key molecule contributing to maintenance of the properties of the dermal sheath cup.

Validation of the cingulate island sign with optimized ratios for discriminating dementia with Lewy bodies from Alzheimer's disease using brain perfusion SPECT.

OBJECTIVE: Dementia with Lewy bodies (DLB) is often cited as the second most common dementia after Alzheimer's disease (AD). It is clinically important to distinguish DLB from AD because specific side effects of antipsychotic drugs are limited to DLB. The relative preservation of cingulate glucose metabolism in the posterior cingulate gyri versus that in the precuni, known as the cingulate island sign (CIS), in patients with DLB compared with AD is supposed to be highly specific for diagnosing DLB. In a previous study, using brain perfusion SPECT, the largest value (0.873) for the area under the receiver operating characteristic (ROC) curve (AUC) for differentiating DLB from AD was obtained with the ratio of the posterior cingulate gyri from an early Alzheimer's disease-specific hypoperfusion volume of interest (VOI) versus the medial occipital lobe. Two purposes of this study are as follows: one is optimization of VOI setting for calculating CIS values and the other is to evaluate their accuracy and simultaneously to retest the method described in our previous paper. METHODS: We conducted a retest of this SPECT method with another cohort of 13 patients with DLB and 13 patients with AD. Furthermore, we optimized VOIs using contrast images obtained from group comparisons of DLB and normal controls; the same 18 patients with DLB and 18 normal controls examined in our previous study. We obtained DLB-specific VOIs from areas where brain perfusion was significantly decreased in DLB. As the numerators of these ratios, early Alzheimer's disease-specific VOIs were used after subtracting DLB-specific VOIs. The DLB-specific VOIs were used as the denominator. RESULTS: In retest, the obtained AUC was 0.858 and the accuracy, sensitivity, and specificity were 84.6, 84.6, and 84.6%, respectively. The ROC curve analysis with these optimized VOIs yielded a higher AUC of 0.882; and the accuracy, sensitivity, and specificity of these new CIS ratios were 84.6, 92.3, and 76.9%, respectively, with a threshold value of 0.281. CONCLUSION: Optimized CISs using brain perfusion SPECT are clinically useful for differentiating DLB from AD.

A study of brain metabolism in fibromyalgia by positron emission tomography.

PURPOSE: The aim of the present study was to determine the brain regions with altered metabolism in patients with treatment-naïve fibromyalgia (FM). METHODS: We used [18F] fluoro-d-glucose positron emission tomography to examine a total of 18 treatment-naïve FM patients and 18 age- and sex-matched healthy controls not suffering from pain. A voxel-by-voxel group analysis was performed using statistical parametric mapping. RESULTS: No significant voxel (peak)-level results were detected in this study; however, some regions were detected as significant-size clusters. There were no significant differences in brain metabolism between FM patients and controls. However, the right thalamus and left lentiform nucleus were hypermetabolic areas in FM patients with poor prognosis compared to the healthy controls. In contrast, the left insula and left lentiform nucleus were hypometabolic areas in FM patients with good prognosis compared to the healthy controls. Compared to FM patients with good prognosis, FM patients with poor prognosis showed significant hypermetabolism in the left thalamus, bilateral lentiform nucleus, and right parahippocampal gyrus. CONCLUSION: The present findings suggest an association between the metabolism in the thalamus, lentiform nucleus, and parahippocampal gyrus and prognosis in FM patients. Further study with a larger number of patients is required to confirm this association.

An automated voxel-based method for calculating the reference value for a brain tumour metabolic index using 18F-FDG-PET and 11C-methionine PET.

OBJECTIVE: The tumour-to-normal ratio (T/N) is a representative index reflecting brain tumour activity by 18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) PET. We proposed a new automated method of calculating the normal reference value (N-value) for use as the denomination of T/N. This method uses voxel-based analysis of FDG- and MET-PET images. We compared the results of this method with those of the standard region-of-interest (ROI) method. METHODS: Data sets were obtained from 32 patients with newly diagnosed glioma and 13 patients with recurrent brain tumour. Our methods were as follows: (1) FDG-PET and MET-PET images were co-registered. (2) The areas where the FDG uptake was higher than a set threshold were selected. (3) For the corresponding areas of MET-PET images, mode and mean voxel values were calculated as tentative MET N-values. (4) Applying the same coordinates to FDG-PET, the voxel values were averaged and used as tentative FDG N-values. (5) The threshold of FDG-PET and whether to use the mode or the mean voxel values were computationally optimized using learning data sets. (6) Applying the optimal threshold and either the mode or mean, N-values of FDG and MET were finally determined. RESULTS: N-values determined by our automated method showed excellent agreement with those determined by a manual ROI method (ICC(2,1) > 0.78). These values were significantly correlated with mean manual N-values (p < 0.001). CONCLUSIONS: Our new method shows sufficiently good agreement with the standard method and can provide a more objective metabolic index.

Differentiation of myocardial ischemia and infarction assessed by dynamic computed tomography perfusion imaging and comparison with cardiac magnetic resonance and single-photon emission computed tomography.

OBJECTIVES: To evaluate the feasibility of myocardial blood flow (MBF) by computed tomography from dynamic CT perfusion (CTP) for detecting myocardial ischemia and infarction assessed by cardiac magnetic resonance (CMR) or single-photon emission computed tomography (SPECT). METHODS: Fifty-three patients who underwent stress dynamic CTP and either SPECT (n = 25) or CMR (n = 28) were retrospectively selected. Normal and abnormal perfused myocardium (ischemia/infarction) were assessed by SPECT/CMR using 16-segment model. Sensitivity and specificity of CT-MBF (mL/g/min) for detecting the ischemic/infarction and severe infarction were assessed. RESULTS: The abnormal perfused myocardium and severe infarction were seen in SPECT (n = 90 and n = 19 of 400 segments) and CMR (n = 223 and n = 36 of 448 segments). For detecting the abnormal perfused myocardium, sensitivity and specificity were 80 % (95 %CI, 71-90) and 86 % (95 %CI, 76-91) in SPECT (cut-off MBF, 1.23), and 82 % (95 %CI, 76-88) and 87 % (95 %CI, 80-92) in CMR (cut-off MBF, 1.25). For detecting severe infarction, sensitivity and specificity were 95 % (95 %CI, 52-100) and 72 % (95 %CI, 53-91) in SPECT (cut-off MBF, 0.92), and 78 % (95 %CI, 67-97) and 80 % (95 %CI, 58-86) in CMR (cut-off MBF, 0.98), respectively. CONCLUSIONS: Dynamic CTP has a potential to detect abnormal perfused myocardium and severe infarction assessed by SPECT/CMR using comparable cut-off MBF. KEY POINTS: • CT-MBF accurately reflects the severity of myocardial perfusion abnormality. • CT-MBF provides good diagnostic accuracy for detecting myocardial perfusion abnormalities. • CT-MBF may assist in stratifying severe myocardial infarction in abnormal perfusion myocardium.

Voxel-based correlation between whole-brain CT perfusion with 320-row area detector ct and iodine 123 iodoamphetamine brain perfusion spect in patients with cerebrovascular disease.

OBJECTIVE: We compared cerebral blood flow (CBF) measured using computed tomographic (CT) perfusion (CTP) and N-isopropyl-p-[(123) I]-iodoamphetamine cerebral perfusion single-photon emission computed tomography (SPECT). METHODS: We used a 320-row area detector CT and N-isopropyl-p-[(123) I]-iodoamphetamine cerebral perfusion SPECT under similar conditions in patients with chronic cerebrovascular disease. Images were automatically aligned 3-dimensionally for voxel-by-voxel comparisons. RESULTS: Linear positive correlations were observed between CTP-CBF including high-blood-flow areas and SPECT-CBF over the whole brain (r = 0.001-0.6, P < 0.01), superior cerebral level (r = 0.45-0.93, P < 0.01), basal ganglia level (r = 0.44-0.77, P < 0.01), and skull base (r = 0.02-0.66, P < 0.01). Correlations between CTP-CBF excluding high-blood-flow areas were significantly higher (P < 0.0001). CONCLUSIONS: Computed tomographic perfusion overestimated CBF compared with SPECT and showed poor correlation at the skull base. Computed tomographic perfusion CTP excluding high-blood-flow areas improved the correlation over the whole brain in patients with chronic cerebrovascular disease.

Isolation of mesenchymal stem cells from human dermis.

Recent studies revealed that mammalian dermis contains multipotent stem cells such as skin-derived precursors (SKPs). SKPs grow in suspension as spheres. In contrast, mesenchymal stem cells (MSCs) are adherent fibroblastic cells. Here, we describe the procedure to isolate MSCs under low-serum culture conditions. In addition, we explain the method to collect MSCs using magnetic cell sorting.

Automatic volumetry of the cerebrospinal fluid space in idiopathic normal pressure hydrocephalus.

OBJECTIVES: To measure the cerebrospinal fluid (CSF) space volume in idiopathic normal pressure hydrocephalus (INPH), we developed a software that allows us to automatically measure the regional CSF space and compared the volumes of the ventricle systems (VS), Sylvian fissures (SF) and sulci at high convexity and midline (SHM) among INPH patients, Alzheimer's disease (AD) patients and healthy volunteers (HVs). METHODS: Fifteen INPH patients, 15 AD patients and 15 HVs were retrospectively selected for this study. 3D-T1 MR images were obtained. We improved upon an automatic gray matter volume system to measure CSF spaces, adopting new regions for the template of INPH-characteristic CSF spaces and measured them. The VS, SF and SHM volumes were calculated relative to the intracranial volume. RESULTS: The relative SHM volume of the INPH group (0.0237 ± 0.0064) was the smallest among the 3 groups (AD: 0.0477 ± 0.0109, HV: 0.0542 ± 0.0045). The VS (0.0499 ± 0.0135) and SF (0.0187 ± 0.0037) volumes of the INPH group were significantly larger than those of the AD (VS: 0.0311 ± 0.0075, SF: 0.0146 ± 0.0026) and HV groups (VS: 0.0167 ± 0.0065, SF: 0.0111 ± 0.017). CONCLUSION: Automatic volume measurement can be used to delineate the characteristic changes in CSF space in patients with INPH and is useful in the diagnosis of INPH.

Voxel-based comparison of preoperative FDG-PET between mesial temporal lobe epilepsy patients with and without postoperative seizure-free outcomes.

OBJECTIVE: This study aims to elucidate differences in preoperative cerebral glucose metabolism between patients who did and did not become seizure free after unilateral mesial temporal lobe epilepsy (mTLE) surgery. We hypothesized that regional glucose metabolism on preoperative fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with seizure-free outcomes differed from that in patients who were not seizure free after appropriate epilepsy surgery for unilateral mTLE. In this study, we compared preoperative FDG-PET findings between these two patient groups by applying a statistical analysis approach, with a voxel-based Asymmetry index (AI), to improve sensitivity for the detection of hypometabolism. METHODS: FDG-PET scans of 28 patients with medically refractory mTLE, of whom 17 achieved a seizure-free outcome (Engel class 1 a-b) during a postoperative follow-up period of at least 2 years, were analyzed retrospectively. Voxel values were adjusted by the AI method as well as the global normalization (GN) method. Two types of statistical analysis were performed. One was a voxel severity analysis with comparison of voxel values at the same coordinate, and the other was extent analysis with comparison of the number of significant voxels in the anatomical areas predefined with Talairach's atlas. RESULTS: In the voxel severity analysis, significant hypometabolism restricted to the ipsilateral temporal tip and hippocampal area was detected in the postoperative seizure-free outcome group as compared to controls. No significant area was detected in the non-seizure-free group as compared to controls (family-wise error corrected, p < 0.05). With extent analysis using a low threshold, the extents of hypometabolism in the ipsilateral hippocampal, frontal and thalamic areas were larger in the seizure-free than in the non-seizure-free group (p = 0.01, 0.03 and 0.01, respectively.) On the other hand, in the contralateral frontal and thalamic areas, extents of hypometabolism were smaller in the seizure-free than in the non-seizure-free group (p = 0.01 and 0.01). CONCLUSIONS: We found the preoperative distribution of hypometabolism to differ between the two patient groups. Severe hypometabolism restricted to the unilateral temporal lobe, with ipsilateral dominant hypometabolism including mild decreases, may support the existence of an epileptogenic focus in the unilateral temporal lobe and a favorable seizure outcome after mTLE surgery.

Hair-inducing ability of human dermal papilla cells cultured under Wnt/ß-catenin signalling activation.

It is well known that dermal papilla cells (DPCs) play crucial roles in hair follicle induction. In this study, we examined whether Wnt/ß-catenin activation results in maintenance of the hair-inducing ability of human DPCs. Expression of DPC marker genes was maintained under Wnt/ß-catenin signalling stimulation by GSK-3ß inhibition. Furthermore, human DPCs showed constant hair induction when transplanted with murine epidermal cell fraction. Alu-positive human DPCs were essentially detected adjacent to the reconstructing epidermal structure positive for P-cadherin immunoreactivity. The transplanted human DPCs were abundant in the surrounding dermal sheath portion of the fully regenerated hair follicles. These results support the importance of Wnt/ß-catenin signalling in hair follicle induction. This study may provide valuable information to establish a culture method of human DPCs for cell-based therapy.

Improvement of the (99m)Tc-ECD brain uptake ratio (BUR) method for measurement of cerebral blood flow.

OBJECTIVE: The brain uptake ratio (BUR) method for the (99m)Tc-ECD SPECT, a non-invasive measurement method of rCBF, has been used in clinical practice in Japan, because it is simple to use. However, the accuracy of this method is limited, as it has problems in the determination of input function and the regression equation. The purpose of this study is to improve the BUR method by reconstructing the determination process of the input function and regression equation based on measurement of the rCBF by H (2) (15) O PET. METHOD: The input function was obtained by setting the region of interest on the ascending aorta instead of the aortic arch. The 3DSRT algorithm was used to obtain the anatomically standardized rCBF, and developed a semi-automatic analyzing software using C++ in order to stabilize the repeatability of the improved BUR (IBUR) method. The regression equation for the IBUR method was obtained by the H (2) (15) O PET rCBFs in 15 patients with the arterial blood sampling method. All the measurements in this study were performed with the patient in the resting state. RESULT: A good correlation was observed between the rCBF values measured by H (2) (15) O PET and the regional BURs measured by the IBUR method (r = 0.86, p < 0.0001). The rCBF values were calculated for only 5 min using a semi-automatic analyzing software. CONCLUSION: The BUR method was improved by changing the location of the input function from the aortic arch to the ascending aorta based on arterial blood flow dynamics, and reconstructing regression equation based on the rCBF values obtained using H (2) (15) O PET. This finding indicates the potential clinical usefulness of this method.