Kazuei Takahashi

Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure

Iodine-123-metaiodobenzylguanidine (123I-MIBG) has been used to assess the integrity and function of the cardiac sympathetic nervous system in patients with heart failure. Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured, and H-FABP has been recently used as a novel marker for the diagnosis of ongoing myocardial damage.ObjectiveThe aim of the present study was to compare cardiac sympathetic nervous activity assessed by123I-MIBG imaging with serum levels of H-FABP in patients with heart failure.MethodsFifty patients with chronic heart failure were studied.123I-MIBG imaging was carried out at 30 min (early) and 240 min (delayed) after the tracer injection. We measured serum levels of H-FABP using a sandwich enzyme linked immunosorbent assay.ResultsHeart to mediastinum (H/M) ratios of123I-MIBG decreased and washout rate increased with higher New York Heart Association (NYHA) functional class. H-FABP, norepinephrine and brain natriuretic peptide (BNP) levels increased as the severity of NYHA class advanced. Delayed H/M ratio was significantly correlated with H-FABP (r = -0.296, p = 0.029) and BNP (r = -0.335, p = 0.0213). Myocardial washout rate of123I-MIBG was also correlated with H-FABP (r = 0.469, p < 0.001), norepinephrine (r = 0.433, p = 0.005), and BNP (r = 0.465, p = 0.001).ConclusionsThese data suggest that cardiac sympathetic nervous activation was associated with ongoing cardiomyocyte damage characterized by an elevated serum level of H-FABP in patients with heart failure.123I-MIBG imaging is an appropriate approach to evaluate non-invasively not only cardiac sympathetic nervous activity, but also latent ongoing myocardial damage in the failing heart.

Dynamic123I-MIBG SPECT reflects sympathetic nervous integrity and predicts clinical outcome in patients with chronic heart failure

Abstract123I-metaiodobenzylguanidine (123I-MIBG) is useful for assessment of the severity and prognosis of patients with chronic heart failure (CHF). To examine123I-MIBG kinetics in the early phase soon after tracer injection, we performed dynamic single photon emission computed tomography (SPECT) in 76 patients with CHF and 17 control subjects. The consecutive 15 images of 2 min-dynamic SPECT were acquired for 30 min after injection. From 0 to 4 min, a significant amount of radioactivity existed in the blood pool, thus we calculated washout rate of123I-MIBG from 4 to 30 min (%WR-E). Patients were followed up with an end-point of cardiac death or re-hospitalization for 16 months (6–30 months). As the NYHA functional class advanced, %WR-E increased (control, NYHA class I, II, and III: 9 ± 4%, 10 ± 5%, 12 ± 5%, and 17 ± 5%*, respectively, *p < 0.01 vs. all other groups). Significant correlation was found between %WR-E and conventional WR from 30 min to 240 min (r = 0.606, p < 0.0001). %WR-E was positively correlated with left ventricular end-diastolic dimension (r = 0.372, p < 0.01 ) and was inversely correlated with left ventricular fractional shortening (r = -0.316, p < 0.02). The normal upper limit of %WR-E was defined as mean + 2SD value of 17 control subjects (17.1%). Patients with abnormally rapid %WR-E levels had a higher cardiac event rate than those with normal %WR-E levels (57% vs. 12%, p < 0.0001). These data suggest that washout rate of123I-MIBG in the early phase from 4 min to 30 min (%WR-E) reflects cardiac sympathetic nervous integrity and is useful to evaluate the severity and prognosis of patients with CHF. The present results indicate a potential role of dynamic SPECT in shortening the123I-MIBG imaging protocol.

Clinical assessment of hepatic functional reserve using99mTc DTPA galactosyl human serum albumin SPECT to prognosticate chronic hepatic diseases —Validation of the use of SPECT and a new indicator—

Rationale: It is generally known that scintigraphy of99mTc diethylenetriamine pentaacetic acidgalactosyl human serum albumin (99mTc-GSA) is useful for assessing hepatic functional reserve. For hepatic functional indicators, the index of the calculated planar image has been used in previous studies. However, there have been few reports that suggest that the indicators calculated from static SPECT data would be useful for the assessment of hepatic function. The aims of this study were to establish a simple method for assessing hepatic functional reserve using the liver SPECT of99mTc-GSA and to apply this method for rich stratification in patients with chronic hepatic diseases.Methods: A liver phantom (a 50% concentration of99mTc solution) was used to compare the planar and SPECT methods. According to the definition of the new indicator, the liver SPECT of99mTc-GSA was divided by a syringe SPECT of99mTc-GSA and was called the liver uptake ratio (LUR). We correlated the LUR and the liver uptake ratio calculated according to the blood-sampling method.99mTc-GSA SPECT was performed in 137 patients with hepatic diseases, including chronic hepatic diseases, and 20 healthy volunteers. The LUR was correlated between the formed subtypes for all subjects.Results: The acquired phantom-count ratio calculated by the SPECT method was more accurate than that acquired by the planar method. A good correlation was obtained between the LUR and the blood-sampling method (r=0.971). The LUR was significantly lower in subjects with severe cirrhosis than in healthy subjects or those with chronic hepatitis and mild cirrhosis, and it was significantly lower in subjects with chronic hepatitis and mild cirrhosis than in healthy subjects. The LUR was significantly correlated with other hepatic function tests. Based on LUR, the chronic hepatic diseases were divided into two groups: Group A, with LURs 30% and higher, and Group B, with LURs below 30%. An LUR of 30% marked the 25th percentile of the mildcirrhosis group. The cumulative survival rates were lower in Group B than in Group A.Conclusion: The SPECT method was superior to the planar method for assessing LURs. LUR was a suitable inducator of99mTc-GSA clearance from the blood pool and of binding to the asialo-glycoprotein receptor. LUR is a simple and clinically useful indicator for the assessment of hepatic functional reserve in chronic hepatic diseases.

Noninvasive identification of left main and three-vessel coronary artery disease by thallium-201 single photon emission computed tomography during adenosine infusion.

Advanced coronary artery disease, defined as left main or three-vessel coronary disease, was identifiable noninvasively by means of adenosine Tl-201 single photon emission tomography. Among 75 consecutive patients with angiographically documented coronary artery disease, there were 11 patients with the presence (group 1) and 64 patients with the absence (group 2) of advanced coronary artery disease. The lung-to-heart ratio (L/H ratio) of Tl-201 uptake was calculated as the fraction of average Tl-201 counts per pixel in the lung divided by those in the myocardium. The left ventricular dilation ratio (LVDR) was determined as a ratio of left ventricular cavity size in the early image to that in the delayed image. The patients in group 1 had more defects (2.3 ± 0.6 seg. vs. 0.9 ± 0.7 seg., p < 0.001), ahigher L/H ratio (35 ± 4% vs. 28 ± 5%, p < 0.001) and a higher LVDR (1.13 ± 0.04 vs. 1.06 ± 0.04, p < 0.001) than those in group 2. The diagnostic accuracy of the identification of advanced coronary artery disease was 89% by perfusion defects, 68% by L/H ratio and 81% by LVDR. Stepwise discriminant analysis revealed that LVDR (F = 36.2, p < 0.0001) and perfusion defects (F = 8.9, p < 0.004) were the significant and independent discriminators of advanced coronary disease.Identification of patients with left main or three-vessel coronary disease was enhanced by additional analysis of cavity dilation of the left ventricle and increased Tl-201 activity in the lung.

Alterations in myocardial perfusion during exercise after isosorbide dinitrate infusion in patients with coronary disease: Assessment by thallium-201 scintigraphy

We studied the effect of intravenous isosorbide dinitrate (ISDN) on myocardial perfusion of patients with coronary artery disease, by using exercise thallium-201 (TI-201) myocardial scintigraphy. A control study was conducted initially to assess regional myocardial perfusion rate. Left ventricular myocardium was divided into six parts: anterior, lateral, apical, inferior, posterior, and septal segments. The segmental myocardial perfusion was characterized according to TI-201 initial uptake index (IUI) of relative distribution and redistribution index (RDI) of TI-201 washout. The normal limit of IUI and RDI was established from the data of 17 persons with normal coronary arteries, and then the IUI less than or equal to 84% and the RDI greater than or equal to 1.12 was defined as abnormal. Based on IUI and RDI, each segment was characterized into three types: A type = IUI less than or equal to 84%, RDI greater than or equal to 1.12; B type = IUI less than or equal to 84%, RDI less than 1.12; and C type = IUI greater than 84%, RDI less than 1.12. ISDN was given as a dose of 0.1 mg/kg/hr, and then treadmill testing was repeated for the same duration of exercise time using the same protocol as in the control period. The segments of A type showed a significant improvement in IUI and RDI after receiving ISDN infusion, while the B and C type segments showed no change. It was also shown that the improvement of IUI and RDI of the A type segments was not as marked in multivessel disease as in cases of single-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged lung retention of 123I-IMP in pulmonary disease

The accumulation of venously injected 123I-IMP in the lung was studied. Between 30 and 50 min after the injection of the 1.5 mCi 123I-IMP, the concentration of 123I-IMP in the broncho-alveolar lavage fluid were much higher than in the blood. It was considered that 123I-IMP was transported into the alveolar spaces and was absorbed by the alveolar cells. The half time (T1/2) of the 123I-IMP release from the lung between 10 and 25 min immediately after the injection was calculated. In normal subjects the T1/2 ranged between 25 and 44 min and was prolonged in subjects with pulmonary fibrosis, sarcoidosis, and allergic alveolitis. It was considered that the retention of 123I-IMP was related not only to the endothelial cells, but also to the alveolar cells. It was considered that the analysis of the lung release of 123I-IMP forms a new lung dysfunction index.

Characteristics of three cases of hepatocellular carcinoma showing enhanced technetium‐99m‐diethylenetriaminepentaacetic acid‐galactosyl human serum albumin accumulation by single photon emission computed tomography analysis

Background:  The asialoglycoprotein receptor (ASGP‐R) is abundantly expressed on the sinusoidal surfaces of hepatocytes. However, the majority of hepatocellular carcinomas (HCC) lack ASGP‐R on their cell surface membranes. We describe three cases of HCC showing increased expression of ASGP‐R in comparison with the surrounding liver tissue.

Coefficient Assignment Approach to Two Disk Mixed Sensitivity Problem of Time-Delay Systems

Abstract This paper presents a control design methodology based on the coeffiocient assignment type techniques without operator-type Riccati equations for two disk mixed sensitivity problem of time delay systems. The key idea is that the sensitivity function and the complementary one are decomposed to the product of two functions. One of them is chosen to satisfy the specifications by the internal model and configuration of poles. The problem is solved by the gain adjustment of the other elements on the basis of coefficient assignment. The systematic design procedure is presented.

Quantitative Assessment of Myocardial 99mTc-sestamibi Uptake During Exercise

An increase of 99mTc-sestamibi uptake in the myocardium during exercise was defined as a response rate, and the feasibility of a response rate for detecting coronary artery disease (CAD) was tested. Eighty-seven patients with suspected CAD had myocardial perfusion imaging with 99mTc-sestamibi during exercise and at rest. A dose of 370 MBq of 99mTc-sestamibi was injected at the maximal level of exercise, and a myocardial image was obtained 90 min later (exercise image). Then, 740 MBq of 99mTc-sestamibi was administered at rest, and myocardial imaging was repeated (rest image). The exercise and rest images were corrected for physical decay and injected doses, and the exercise image was subtracted from the rest image to obtain the corrected rest image. A response rate was calculated as follows: (exercise image-corrected rest image)x100/corrected rest image (%). The global response rates of 20 patients without significant coronary stenosis (< or =50%) were higher than those of 67 patients with significant coronary stenosis (81+/-33% and 50+/-28%, p<0.01). Global response rates were correlated with the maximal rate pressure products during exercise (r=0.56, p<0.01) and delta rate pressure products (r=0.53, p<0.01). Regional response rates in myocardial areas perfused by stenotic coronary arteries of < or =50%, 75%, 90% and 99-100% were 60+/-24%,* 56+/-33%,* 40+/-23%* and 30+/-23%,* respectively, (*p<0.01 vs without significant coronary stenosis). The response rates decreased as the severity of coronary artery stenosis advanced, and distinguished between coronary stenoses of graded severity. Accordingly, the response rate from myocardial perfusion imaging with 99mTc-sestamibi may provide complementary information to the conventional inspection with myocardial tomography regarding the severity of CAD.

Improvement of data acquisition and analysis to evaluate regional ventilation

To evaluate the regional ventilation using 133Xe under different conditions, the respiratory flow and the phase with image were measured simultaneously, and sequential frames were made breath by breath. The flow signal and phase signal were converted to pulse signals by a microcomputer and stored with image data in the same file. Thus, the tidal volume and duration of each breath were measured. From sequential frames compiled breath by breath, an activity breath-number curve was made in each pixel, and the half-clearance breath number (B1/2) was calculated. The changes in conventional half-clearance time (T1/2) and B1/2 were compared under different ventilatory conditions in normal subjects and in patients with chronic pulmonary emphysema. Values of B1/2 indicated the change of turnover rate more accurately than T1/2. It is considered that B1/2 is a better parameter than T1/2 for evaluating the change in regional ventilatory function under different conditions.