Shin-ichiro Kumita

Development of quantitative analysis method for stereotactic brain image : Assessment of reduced accumulation in extent and severity using anatomical segmentation

Through visual assessment by three-dimensional (3D) brain image analysis methods using stereotactic brain coordinates system, such as three-dimensional stereotactic surface projections and statistical parametric mapping, it is difficult to quantitatively assess anatomical information and the range of extent of an abnormal region. In this study, we devised a method to quantitatively assess local abnormal findings by segmenting a brain map according to anatomical structure. Through quantitative local abnormality assessment using this method, we studied the characteristics of distribution of reduced blood flow in cases with dementia of the Alzheimer type (DAT). Using twenty-five cases with DAT (mean age, 68.9 years old), all of whom were diagnosed as probable Alzheimers disease based on NINCDS-ADRDA, we collected I-123 iodoamphetamine SPECT data. A 3D brain map using the 3D-SSP program was compared with the data of 20 cases in the control group, who age-matched the subject cases. To study local abnormalities on the 3D images, we divided the whole brain into 24 segments based on anatomical classification. We assessed the extent of an abnormal region in each segment (rate of the coordinates with a Z-value that exceeds the threshold value, in all coordinates within a segment), and severity (average Z-value of the coordinates with a Z-value that exceeds the threshold value). This method clarified orientation and expansion of reduced accumulation, through classifying stereotactic brain coordinates according to the anatomical structure. This method was considered useful for quantitatively grasping distribution abnormalities in the brain and changes in abnormality distribution.

Therapeutic angiogenesis by autologous bone marrow cell implantation for refractory chronic peripheral arterial disease using assessment of neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy.

We investigated efficacy and safety of implantation of autologous bone marrow mononuclear cells plus platelets, including endothelial progenitor cells (EPCs), for recovering refractory chronic peripheral arterial disease (PAD) using visual and quantitative analyses by 99mTc-tetrofosmin (TF) perfusion scintigraphy, and also investigated various quantitative assessments objectively. We performed 12 consecutive cases and 19 limbs and hands with severe chronic PAD that were almost Fontaine class IV (11/12 cases, about 92%) in this trial. This treatment was very effective in relieving severe pain of PAD, especially for Buergers disease. We used a visual analog scale (VAS) for measurement of pain level. The maximum pain level before implantation was 66.5 ± 5.0 mm, and it decreased to 12.1 ± 2.2 mm after implantation (p < 0.001). Rest pain in legs and fingers was resolved in 11 cases (11/12 cases, 92%). All patients could measure pain-free walking time on a treadmill, which improved remarkably (140 ± 53 s before implantation vs. 451 ± 74 s after implantation, p = 0.034). Resting ankle brachial pressure index (ABI) in legs implanted with bone marrow mononuclear cells was also improved (0.65 ± 0.08 before implantation vs. 0.73 ± 0.07 after implantation, p = 0.055). According to 99mTc-TF perfusion scintigraphy, the proximal area (region from knee to ankle) was 1.32 ± 0.10 before implantation versus 1.56 ± 0.11 after implantation (p = 0.007). 99mTc-TF perfusion scintigraphy in the distal area (region from ankle to end of toes, or from wrist to end of fingers) was 0.79 ± 0.06 before implantation versus 0.83 ± 0.06 after implantation (p = 0.29). Ischemic legs and hands that were injected showed increased perfusion blood flow. 99mTc-TF perfusion scintigraphy was effective to estimate visual and quantitative analysis of collateral vessels in neovascularization. We were successful with this new treatment for the most severe, chronic PAD that was not curable by any of the current treatments. Thus, this therapeutic angiogenesis could be a new strategy for saving severe ischemic limbs and hands.

Three-dimensional display in staging hemodynamic brain ischemia for JET study : Objective evaluation using SEE analysis and 3D-SSP display

The Japanese EC-IC bypass trial (JET study) was established to evaluate the validity of MCA-STA anastomosis in intracranial arterial occlusive disease aiming at stroke prevention. This study must use an objective method to reliably estimate hemodynamic brain ischemia. We devised a method of objectively classifying the severity of hemodynamic ischemia using quantitatively analytical and display software, stereotactic extraction estimation for stereotactic brain coordinates and three-dimensional stereotactic surface projections (3D-SSP). We analyzed data from 16 patients registered in the JET study. Our method offers quantitative information and 3-dimensional displays of the CBF at rest and after Diamox challenge, vascular reserve and the severity of the hemodynamic brain ischemia. We compared the maximal projection counts with ROI data from tomographic images in the anterior commissure-posterior commissure plane. The maximal counts data correlated closely with the ROI data of rest and with Diamox SPECT images (both p < 0.0001). The slopes of the linear regression line were 1.15 and 1.12, respectively. The results of this study indicated that our method could simply and objectively evaluate the severity of impaired brain circulation. This procedure should support the evaluation of hemodynamic ischemia in the JET study although validation is required by several institutions using more study subjects.

Recommendations for (18)F-fluorodeoxyglucose positron emission tomography imaging for cardiac sarcoidosis: Japanese Society of Nuclear Cardiology recommendations.

Sarcoidosis is a systemic granulomatous disease that forms epithelioid cell granuloma (accompanied by infiltration of inflammatory cells) without caseous necrosis in organs throughout the body, including the lungs, lymph nodes, skin, eyes, heart, and muscles. Generally there is a good prognosis for spontaneous resolution of sarcoidosis; however, for cardiac-involvement sarcoidosis, the prognosis is extremely poor, and careful management is required. The most common cause of death from sarcoidosis is cardiac complications of the disease, and therefore early detection and treatment of these are very important in the management of cardiac-involvement sarcoidosis. Guidelines for the diagnosis of cardiac sarcoidosis were first published by Hiraga et al. [1] in 1992 (Table 1). These guidelines were modified by the joint committee of the Japan Society of Sarcoidosis and Other Granulomatous Disorders and the Japanese College of Cardiology in 2006 (Table 2) [2]. These modified guidelines stipulate the following: a histopathological or clinical diagnosis of sarcoidosis in organs other than the heart is essential, and the following cases should be diagnosed as cardiac sarcoidosis: (1) cases histopathologically diagnosed as positive for cardiac sarcoidosis on the basis of myocardial biopsy (histopathologically diagnosed group) and (2) cases with clinical findings indicating characteristic cardiac abnormalities including principal and secondary signs and symptoms (clinically diagnosed group) (Tables 1, 2). In the histopathologically diagnosed group, the positivity rate for detection of cardiac sarcoidosis may be low owing to sampling errors in myocardial biopsy. Hence, in actual clinical settings, the number of cases in the clinically diagnosed group is higher than in the histopathologically diagnosed group. Upon diagnosis of cardiac sarcoidosis, it is important to determine the disease activity to develop a treatment strategy, assess severity, predict prognosis, and Committee for diagnosis of cardiac sarcoidosis using 18F-FDG PET, Japanese Society of Nuclear Cardiology.

Contrast-enhanced myocardial T1-weighted scout (Look–Locker) imaging for the detection of myocardial damages in hypertrophic cardiomyopathy

To assess the myocardial damage in hypertrophic cardiomyopathy (HCM) using contrast‐enhanced myocardial T1‐weighted scout (Look–Locker) magnetic resonance imaging (MRI).

Non–contrast-enhanced MR angiography of the thoracic aorta using cardiac and navigator-gated magnetization-prepared three-dimensional steady-state free precession

To assess the usefulness of non–contrast‐enhanced MR angiography using cardiac and navigator‐gated magnetization‐prepared three‐dimensional (3D) steady‐state free precession (SSFP) imaging for the diagnosis of diseases of the thoracic aorta.

Association Between Abnormal Myocardial Fatty Acid Metabolism and Cardiac-Derived Death Among Patients Undergoing Hemodialysis: Results From a Cohort Study in Japan

BACKGROUND Detecting myocardial ischemia in hemodialysis patients is crucial given the high incidence of silent ischemia and the high cardiovascular mortality rates. Abnormal myocardial fatty acid metabolism as determined by imaging with (123)I-labeled BMIPP (β-methyl iodophenyl-pentadecanoic acid) might be associated with cardiac-derived death in hemodialysis patients. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS Asymptomatic hemodialysis patients with one or more cardiovascular risk factors, but without known coronary artery disease, were followed up for 3 years at 48 Japanese hospitals (406 men, 271 women; mean age, 64 years). PREDICTOR Baseline BMIPP summed scores semiquantified using a 17-segment 5-point system (normal, 0; absent, 4). OUTCOMES Cardiac-derived death, including cardiac and sudden death. MEASUREMENTS HRs were estimated using a Cox model for associations between BMIPP summed scores and cardiac-derived death, adjusting for potential confounders of age, sex, body mass index, dialysis duration, and cardiovascular risk factors. RESULTS Rates of all-cause mortality and cardiac-derived death were 18.5% and 6.8%, respectively. Cardiac-derived death (acute myocardial infarction [n = 10], congestive heart failure [n = 13], arrhythmia [n = 2], valvular heart disease [n = 1], and sudden death [n = 20]) accounted for 36.8% of all-cause deaths. Cardiac-derived death (n = 46) was associated with age, history of heart failure, and BMIPP summed scores of 4 or higher (HR, 2.9; P < 0.001). Three-year cardiac-derived death-free survival rates were 95.7%, 90.6%, and 78.8% when BMIPP summed scores were 3 or lower, 4-8, and 9 or higher, respectively. BMIPP summed score also was a predictor of all-cause death (HR, 1.6; P = 0.009). LIMITATIONS Sudden death of unknown cause was considered to have been cardiac derived, although a coronary origin was not confirmed. CONCLUSIONS Abnormal myocardial fatty acid metabolism is associated with cardiac-derived death in hemodialysis patients. BMIPP single-proton emission computed tomography appears clinically useful for predicting cardiac-derived death in this population.

Significant suppression of myocardial 18F-fluorodeoxyglucose uptake using 24-h carbohydrate restriction and a low-carbohydrate, high-fat diet

OBJECTIVES (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a useful tool for evaluating inflammation. Because, myocardial-FDG uptake occurs with diverse physiology, it should be suppressed during evaluation of myocardial inflammation by FDG-PET/CT. Diets inducing fat-based metabolism, such as a low-carbohydrate, high-fat diet (LCHF), are used in uptake-suppression protocols. However, a complete suppression of myocardial-FDG uptake has not been established. Hence, we assessed the efficacy of 24-h carbohydrate restriction along with an LCHF diet compared to that of the conventional protocol in suppressing myocardial-FDG uptake and also compared fat and glucose metabolism between these protocols. METHODS Fourteen healthy volunteers agreed to undergo >24-h carbohydrate restriction (glucose, <10g) and drank an LCHF beverage an hour before FDG administration. A scan performed under conventional fasting protocol served as the control. The maximal standardized uptake values (SUVmax) of the left ventricular (LV) myocardium, and left atrium lumen (blood pool), liver, and lung fields as background, were measured. Blood sugar, free fatty acids (FFAs), insulin, and triglyceride concentrations were measured just before FDG injection and compared between the 2 protocols. RESULTS Global LV myocardial uptake was significantly lower with the diet-preparation protocol (SUVmax 1.31 [1.15-1.49] vs. 2.98 [1.76-6.43], p=0.001). Target-to-background ratios [myocardium-to-blood ratio (MBR), myocardium-to-lung ratio (MLR), and myocardium-to-liver ratio (MLvR)] were also significantly lower with the diet-preparation protocol [MBR: 0.75 (0.68-0.84) vs. 1.63 (0.98-4.09), p<0.001; MLR: 1.87 (1.53-2.47) vs. 4.54 (2.53-12.78), p=0.004; MLvR: 0.48 (0.44-0.56) vs. 1.11 (0.63-2.32), p=0.002]. Only insulin levels were significantly different between the subjects in each protocol group (11.3 [6.2-15.1] vs. 3.9 [2.9-6.2]). CONCLUSION Carbohydrate restriction together with an LCHF supplement administered 1h before FDG significantly suppressed myocardial-FDG uptake. FFAs and insulin might not directly affect myocardial-FDG uptake.

FDG-PET/CT in the diagnosis of recurrent breast cancer

Background An advantage of PET/CT has been demonstrated for diagnosis of several tumor entities. In patients with breast cancer, early diagnosis and accurate restaging of recurrence after surgery is important for selection of the most appropriate therapeutic strategy. Purpose To evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG), for follow-up of patients with suspected recurrent breast cancer. Material and Methods Forty-seven patients with suspected recurrent breast cancer underwent PET/CT. The PET and PET/CT images were interpreted without knowledge of the results of other diagnostic modalities, and compared with each other with reference to the final diagnosis. Results Twenty-five (53%) patients suffered tumor recurrence. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 96%, 91%, 92%, 95%, and 94%, respectively. In comparison with PET, PET/CT had a higher sensitivity and accuracy (96% vs. 80% and 94% vs. 81%, respectively). The difference in diagnostic accuracy between PET/CT and PET was significant (P < 0.05). Conclusion The present findings indicate that PET/CT is an accurate, sensitive and reliable modality for screening and detection of breast cancer recurrence. PET/CT appears to be an effective surveillance tool, as it is able to cover the whole body in a single procedure and shows good performance.

Stereotactic statistical imaging analysis of the brain using the easy Z-score imaging system for sharing a normal database

Statistical brain imaging analysis has good objectivity and reproducibility. In Japan, statistical parametric mapping (SPM) and three-dimensional stereotactic surface projections (3D-SSP) are used nationwide as statistical imaging analysis with standard brain coordinates. They often help to interpret brain single photon emission computed tomography (SPECT) images by avoiding possible pitfalls (e.g., effects of aging, atrophy) with which clinicians are unfamiliar. However, this type of analysis presents a problem: statistical processing requires many normal subject images. The easy Z-score imaging system (eZIS) is one of the statistical analysis methods that uses SPM processing in normalization and smoothing, and it has the function of image conversion leading to statistical analysis without a control database. Therefore, statistical analysis can be used in clinical practice by sharing a prepared normal database. By unifying the image quality by processing a shared database, this program has great potential for sharing patient imaging data in many hospitals. It is expected that the eZIS will help perform detailed analysis in many functional diseases in collaborative studies. This article describes the interpretation of brain SPECT images and suggests the usefulness and potential of eZIS.