Naoya Hattori

Assessment of regional and global left ventricular function by reinjection Tl-201 and rest Tc-99m sestamibi ECG-gated SPECT: Comparison with three-dimensional magnetic resonance imaging

OBJECTIVES The purpose of this study was to test the ability of reinjection thallium-201 and rest technetium-99m sestamibi ECG (electrocardiographic)-gated SPECT (i.e., reinjection-g-SPECT [single-photon emission computed tomography] and MIBI-g-SPECT) to determine regional and global functional parameters. BACKGROUND The ECG-gated perfusion SPECT was reported to provide accurate left ventricular ejection fraction (LVEF) using an automated algorithm. We hypothesized that other various functional data may be obtained using reinjection-g-SPECT and MIBI-g-SPECT. METHODS Reinjection-g-SPECT, MIBI-g-SPECT, and three-dimensional magnetic resonance imaging (3DMRI) were conducted in 20 patients with coronary artery disease. Regional wall motion (RWM) and wall thickening (RWT) were analyzed using semiquantitative visual scoring by each g-SPECT and 3DMRI. The left ventricular end-systolic and end-diastolic volumes (EDV, ESV) and LVEF estimated by reinjection- and MIBI-g-SPECT were compared with the results of 3DMRI. RESULTS A high degree of agreement in RWM and RWT assessment was observed between each g-SPECT and 3DMRI (kappa >.70, p < .001). The LVEF values by reinjection- and MIBI-g-SPECT correlated and agreed well with those by 3DMRI (reinjection: r = .92, SEE = 5.9%, SD of differences = 5.7%; sestamibi: r = .94, SEE = 4.4%, SD of differences = 5.1%). The same also pertained to EDV (reinjection: r = .85, SEE = 18.7 ml, SD of differences = 18.4 ml; sestamibi: r = .92, SEE = 13.1 ml, SD of differences = 13.0 ml) and ESV (reinjection: r = .94, SEE = 10.3 ml, SD of differences = 10.3 ml; sestamibi: r = .97, SEE = 6.7 ml [p < .05 vs. reinjection by F test], SD of differences = 6.6 ml [p < .05 vs. reinjection by F test]). CONCLUSIONS Reinjection- and MIBI-g-SPECT provide clinically satisfactory various functional data. These functional data in combination with the perfusion information will improve diagnostic and prognostic accuracy without an increase in cost or the radiation dose to the patients.

Selective Metabolic Reduction in Gray Matter Acutely following Human Traumatic Brain Injury

The aim of this study was to determine whether the apparent loss of overall gray-white matter contrast (GM/WM) seen on FDG-PET imaging reflects the differential changes of glucose metabolic rate (CMRglc) in cortical gray mater (GM) and subcortical white mater (WM) following TBI. The clinical significance of the CMRglc GM-to-WM ratio was also evaluated. Nineteen normal volunteers and 14 TBI patients were studied. Each subject had a quantitative FDG-PET, a quantitative H215O-PET and a MR scan acutely following TBI. Stabilities of the global and regional FDG lumped constants (LC) were studied. Parametric images (pixel unit: mg/min/100g) of FDG uptake rate (CURFDG) and CMRglc were generated. The changes of CMR(glc) in whole brain, GM and WM were studied separately by using a MRI-segmentation-based technique. The GM-to-WM ratios of both CURFDG and CMRglc images were significantly (p < 0.001) decreased (>31%) in TBI patients. The global LC value reduced significantly (p < 0.01) in TBI patients. The CMRglc decreased significantly (p < 0.001) in GM but not in WM (p > 0.1). Kinetic analysis revealed significant (p < 0.001) decrease of GM hexokinase activity in TBI patients. The GM-to-WM ratios of CMRglc correlated (r = 0.64) with the initial Glasgow Coma Score (GCS) of TBI patients. The patients with higher CMRglc GM-to-WM ratios (>1.54) showed good recovery 12 months after TBI. There was a selective CMRglc reduction in cortical GM following TBI. The pathophysiological basis for the reduction in GM-to-WM CMRglc ratio seen on FDG-PET imaging following TBI remains to be determined.

Use of technetium-99m sestamibi ECG-gated single-photon emission tomography for the evaluation of left ventricular function following coronary artery bypass graft : comparison with three-dimensional magnetic resonance imaging

Abstract. In patients who had undergone cardiac surgery (coronary artery bypass graft) and whose hearts showed abnormal movement during the cardiac cycle, we studied the accuracy of functional assessment using ECG-gated single-photon emission tomography (SPET) and the automated software developed by Germano et al. by comparing the findings with magnetic resonance (MR) images acquired three-dimensionally. Sixteen patients who had undergone cardiac surgery underwent 99mTc-sestamibi gated SPET (MIBI-g-SPET) and MRI on the same day. Left ventricular end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (LVEF) were measured using MIBI-g-SPET and the aforementioned algorithm. Regional wall thickening was assessed using a four-point scale on MIBI-g-SPET and cine MRI. There was a good correlation between MIBI-g-SPET and MRI in respect of EDV (r=0.89), ESV (r=0.93) and LVEF (r=0.89). A high degree of agreement was found between the wall thickening scores obtained by MIBI-g-SPET and MRI in total segments (κ=0.62) and in septal segments (κ=0.67). It is concluded that ECG-gated perfusion SPET can provide regional and global functional information, including absolute volumes, in patients following cardiac surgery.

Prognostic value of iodine-123 labelled BMIPP fatty acid analogue imaging in patients with myocardial infarction

This study was undertaken to evaluate the prognostic value of iodine-123 labelled 15-iodophenyl3-R,S-methyl pentadecanoic acid (BMIPP) imaging in patients with myocardial infarction. BMIPP is an iodinated methyl branched fatty acid analogue which is trapped in the myocardium with little washout, thereby reflecting fatty acid utilization in the myocardium. We previously reported that in patients with myocardial infarction, regions are often observed where reduced BMIPP uptake is seen relative to thallium-201 perfusion at rest. However, the clinical significance of such discordant BMIPP uptake remains unknown. Fifty consecutive patients with chronic myocardial infarction referred for stress thallium scan and coronary arteriography underwent BMIPP imaging at rest. Each patient was in a stable condition at the time of the radionuclide study. Follow-up was performed at a mean interval of 23 months to investigate the prognostic implications of the radionuclide studies. Nine patients had cardiac events during the follow-up period. Univariate analysis showed that the number of discordant BMIPP versus201TL uptake segments was the best predictor of future cardiac events (P=0.0245), followed by the presence of discordant BMIPP uptake (P=0.0388) and the number of201TL redistribution segments (P=0.0444). When all the clinical and radionuclide variables were analysed by Cox regression analysis, the presence of discordant BMIPP uptake was the best, and an independent, predictor of future cardiac events (χ2=8.5) followed by the number of coronary stenoses on angiography (χ2=3.9). These preliminary data suggest that decreased BMIPP uptake relative to201TL is a valuable predictor of future cardiac events in patients with myocardial infarction. Areas with such discordant BMIPP uptake may contain jeopardized myocardium where fatty acid utilization has been severely suppressed relative to myocardial perfusion.

Subcortical white matter metabolic changes remote from focal hemorrhagic lesions suggest diffuse injury after human traumatic brain injury.

OBJECTIVE:We used positron emission tomographic studies to prospectively examine the relationship between glucose and oxidative metabolism in the subcortical white matter (WM) acutely after traumatic brain injury (TBI). The objective was to determine the nature, extent, and degree of metabolic abnormalities in subcortical brain regions remote from hemorrhagic lesions. METHODS:Sixteen normal volunteers and 10 TBI patients (Glasgow Coma Scale score, 4–10; age, 17–64 yr; 6 with focal and 4 with diffuse injury) were studied. Each subject underwent dynamic positron emission tomographic studies using [15O]CO, 15O2, [15O]H2O, and fluorodeoxyglucose plus a magnetic resonance imaging scan acutely after TBI. Parametric images of the metabolic rate of oxygen and metabolic rate of glucose were generated, and a molar oxygen-to-glucose utilization ratio was calculated. Data from gray matter and WM remote from hemorrhagic lesions, plus whole brain, were analyzed. RESULTS:There was a significant reduction in the subcortical WM oxygen-to-glucose utilization ratio after TBI compared with normal values (3.99 ± 0.77 versus 5.37 ± 1.00; P < 0.01), whereas the mean cortical gray matter and whole-brain values remained unchanged. WM metabolic changes, which were diffuse throughout the hemispheres, were characterized by a reduction in the metabolic rate of oxygen without a concomitant drop in the metabolic rate of glucose. CONCLUSION:The extent and degree of subcortical WM metabolic abnormalities after moderate and severe TBI suggest that diffuse WM injury is a general phenomenon after such injuries. This pervasive finding may indicate that the concept of focal traumatic injury, although valid from a computed tomographic imaging standpoint, may be misleading when considering metabolic derangements associated with TBI.

Regional heterogeneity of post-traumatic brain metabolism as studied by microdialysis, magnetic resonance spectroscopy and positron emission tomography

INTRODUCTION Traumatic brain injury (TBI) results in primary damage to selected brain regions immediately or within a few minutes. is injury is generally easily recognized on computerized tomographic scans taken in the emergency room, and is often the target of emergency surgery. However, adjacent tissue may be variably damaged in the acute process or as a result of secondary insults. e pathological changes in this adjacent tissue have been best characterized by imaging (11-13) and by studies of brain metabolism (4). In addition, widespread disturbances of brain metabolism with regional heterogeneity exist after experimental TBI and human TBI. e significance of focal pathology on the metabolism of the surviving surrounding brain tissue is not well appreciated. Unfortunately, this regional variation of metabolism may not be static and may change over time (3). us, monitoring brain metabolism during the acute injury period is difficult to do with neuroimaging alone. e ability to selectively monitor surrounding tissue has recently been studied using positron emission tomography (2, 7, 10) and continuous monitoring may be possible using cerebral microdialysis (5, 9, 10, 14, 18). Cerebral microdialysis offers an indirect method of monitoring brain metabolism by looking at changes in the extracellular substrates and products of metabolism. e enhanced temporal resolution of cerebral microdialysis is offset by the confined regional specificity of the technique, with a sampling tissue volume of 1 to 2 cm3. However, strategically placed microdialysis catheters may offer continuous monitoring of a specific region of interest over time. e purpose of this paper is to delineate, using 3 case examples, the ability of cerebral microdialysis to provide continuous monitoring of regionally heterogeneous brain glucose metabolism. Regional neurochemical heterogeneity of glucose metabolism is confirmed by using fluorodeoxyglucose positron emission tomography (FDGPET) and proton-magnetic resonance spectroscopy (H-MRS).

Recent advances in nuclear cardiology in the study of coronary artery disease

A variety of new radiopharmaceutical agents have been introduced to probe myocardial functionin vivo. This review will introduce these new techniques which have recently been available in Japan. Tc-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use of first-pass angiography or ECG-gated acquisition. Positron emission tomography enables metabolic assessmentin vivo. Preserved FDG uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently I-123 BMIPP, a branched fatty acid analog, has been clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. Such perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Both of them are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. I-123 MIBG uptake in the myocardium reflects adrenergic neuronal functionin vivo. In the study of coronary artery disease, neuronal denervation is often observed around the infarcted myocardium and post ischemic region as well. More importantly, reduced MIBG uptake in these patients can identify high risk for ventricular arrhythmias and assess severity of congestive heart failure. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment in these patients.

PET investigation of post-traumatic cerebral blood volume and blood flow.

Hemodynamic changes following traumatic brain injury (TBI) may reflect cellular damage leading to secondary injury. The purpose of this study was to investigate the regional hemodynamic parameters acutely after TBI among regions in and around contusions. Sixteen patients (11 male, 5 female) showing evidence of contusion on CT and 18 normal volunteers (12 male, 6 female) underwent positron emission tomography (PET) with O-15 CO and O-15 H2O to estimate cerebral blood volume (CBV) and cerebral blood flow (CBF), respectively. A flow to volume ratio (FVR = CBF/CBV) was also calculated as an index of vasodilatation. The hemodynamic parameters were compared among contusion, pericontusion, and remote areas. Globally, hemodynamic parameters did not differ between patients and normal volunteers, and did not correlate with intracranial pressure (ICP). Regionally, contusional and pericontusional areas showed significantly lower CBF and FVR compared with normal volunteers, while CBV did not differ significantly. The correlation between CBF and CBV was significant (r = 0.37, p < 0.01). Remote areas did not show a significant difference in any of the PET parameters. In conclusion, regional brain edema is likely to occur in contusion and pericontusion areas, while some of the contusional tissue may show vascular engorgement.

Diagnostic Accuracy of Lymph Node Metastasis Depends on Metabolic Activity of the Primary Lesion in Thoracic Squamous Esophageal Cancer

The metabolic activity of the primary tumor is an important variable in 18F-FDG PET interpretation for presurgical staging, because this activity is likely to affect the possibility of detection of malignant involvement in lymph nodes (LNs). The purpose of this study was to reevaluate the diagnostic accuracy of 18F-FDG PET/CT for the presurgical staging of esophageal squamous cell carcinoma (SCC) in correlation with the 18F-FDG avidity of the primary lesions. Methods: One hundred fifty-six patients (mean age ± SD, 61.4 ± 8.0 y) underwent 18F-FDG PET/CT before surgical esophagectomy and LN dissection. LN metastasis was identified using the fusion of PET and CT images with increased 18F-FDG uptake greater than the background activity of the adjacent structures. The results of the patients’ 18F-FDG PET/CT examinations for LN involvement were compared with the histopathologic results to investigate the diagnostic accuracy of 18F-FDG PET/CT for tumor staging. In addition, we examined the correlation between the diagnostic accuracy of 18F-FDG PET/CT for LN involvement and the 18F-FDG avidity of the primary lesions, to investigate the effect of tumor aggressiveness on the diagnosis of LN metastasis. Results: The diagnostic accuracy of 18F-FDG PET/CT for LN metastasis showed a low sensitivity, ranging from 29.3% to 53.3%, whereas the specificity was higher than 89.8% in regional thoracic nodes and in remote areas of the cervical and abdominal regions. The 18F-FDG uptake of the primary lesions positively correlated with that of the metastatic LNs in the thoracic field (R = 0.52, P < 0.05). As a result, our receiver-operating-characteristic analyses demonstrated an area under the curve value of 0.73, with the optimal cutoff value at a maximum standardized uptake value of 3.3 in patients with mid to high 18F-FDG avidity in the primary lesions (maximum standardized uptake value ≥ 5). Conclusion: This study showed that the avidity of the primary esophageal SCCs affected the detectability of lymph nodal metastases. If primary lesions of esophageal SCC present with a low 18F-FDG uptake, PET/CT may have a limited role for initial staging because of low sensitivity to detect lymph node metastases.

Simplified quantification of regional cerebral blood flow with99mTc-ECD SPECT and continuous arterial blood sampling

The goal of this study was to develop a simple method for quantification of regional cerebral blood flow (rCBF) with99mTc-ethyl cysteinate dinier (ECD) SPECT. Following an intravenous constant infusion of ECD for one minute, serial dynamic SPECT imaging was performed for 40 minutes in 6 healthy male volunteers with intermittent arterial blood sampling. PET scan with15O-water was performed on the same day before the SPECT study for measurement of rCBF. Arterial blood data demonstrated rapid conversion of ECD to the hydrophilic metabolites, and most of the arterial input to the brain was completed within 5 minutes after the injection. Brain activity reached a peak value soon after the cessation of infusion, and was stable thereafter with very little washout. Net extraction of ECD in the brain calculated by arterial input of ECD and rCBF demonstrated a rapid decrease within a few minutes, reaching 42.7% at 5 minutes. The simulation study suggested that the arterial blood activity obtained by continuous drawing for 5 minutes and a single SPECT scan would provide a reasonable estimate of rCBF under the assumption of constant net extraction in the brain.