Hitoshi Naruse

Correction of nonuniform attenuation and image fusion in SPECT imaging by means of separate X-ray CT

Improvements in image quality and quantitation measurement, and the addition of detailed anatomical structures are important topics for single-photon emission tomography (SPECT). The goal of this study was to develop a practical system enabling both nonuniform attenuation correction and image fusion of SPECT images by means of high-performance X-ray computed tomography (CT). A SPECT system and a helical X-ray CT system were placed next to each other and linked with Ethernet. To avoid positional differences between the SPECT and X-ray CT studies, identical flat patient tables were used for both scans; body distortion was minimized with laser beams from the upper and lateral directions to detect the position of the skin surface. For the raw projection data of SPECT, a scatter correction was performed with the triple energy window method. Image fusion of the X-ray CT and SPECT images was performed automatically by auto-registration of fiducial markers attached to the skin surface. After registration of the X-ray CT and SPECT images, an X-ray CT-derived attenuation map was created with the calibration curve for99mTc. The SPECT images were then reconstructed with scatter and attenuation correction by means of a maximum likelihood expectation maximization algorithm. This system was evaluated in torso and cylindlical phantoms and in 4 patients referred for myocardial SPECT imaging with Tc-99m tetrofosmin. In the torso phantom study, the SPECT and X-ray CT images overlapped exactly on the computer display. After scatter and attenuation correction, the artifactual activity reduction in the inferior wall of the myocardium improved. Conversely, the increased activity around the torso surface and the lungs was reduced. In the abdomen, the liver activity, which was originally uniform, had recovered after scatter and attenuation correction processing. The clinical study also showed good overlapping of cardiac and skin surface outlines on the fused SPECT and X-ray CT images. The effectiveness of the scatter and attenuation correction process was similar to that observed in the phantom study. Because the total time required for computer processing was less than 10 minutes, this method of attenuation correction and image fusion for SPECT images is expected to become popular in clinical practice.

Prediction of functional recovery and prognosis in patients with acute myocardial infarction by123I-BMIPP and201Tl myocardial single photon emission computed tomography: A multicenter trial

Abstract123I-BMIPP [15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid] was developed for metabolic imaging with SPECT. A multicenter collaborative study was conducted on a large patient series to determine whether123I-BMIPP and201Tl myocardial SPECT are of use in predicting the prognosis and ventricular function after acute myocardial infarction (AMI). Patients with uncomplicated first AMI underwent resting123I-BMIPP and201Tl myocardial SPECT in the subacute phase after the onset of AMI. Of these, 167 patients who had been followed up for an average of 22 months were retrospectively reviewed to predict serious cardiac events and recurrent ischemia. In addition, the association between changes in radionuclide parameters and recurrent ischemia was investigated in Subgroup A (58 patients) who had repeated SPECT in the chronic phase. Furthermore, prediction of the ejection fraction (EF) was investigated in Subgroup B (94 patients) and Subgroup C (76 patients) in whom left ventriculography was performed at the time of discharge and 90 days or more after the onset, respectively. The prognosis was generally favorable, with 4 cases of cardiac death (2%), 3 of heart failure (2%), 4 of nonfatal reMI (2%), and 25 of recurrent ischemia (15%). The results of Cox multivariate regression analysis revealed a high probability of serious cardiac events in patients who were elderly (p = 0.04), who had 90% or more residual stenosis of the infarct-related artery (p = 0.09), and who had a high BMIPP defect score (p = 0.17). There was a high probability of recurrent ischemia in elderly patients (p = 0.10) who had multi-vessel disease (p = 0.03), but no association was found with radionuclide parameters in the subacute phase. In Subgroup A, however, the probability of recurrent ischemia tended to be high in patients with a large mismatch score between123I-BMIPP and201Tl in the subacute to chronic phase. An important observation was that the extent of BMIPP defect was more strongly correlated with EF at the time of discharge and 90 days or more after the onset than the extent of Tl defect (r = −0.60 vs. r = −0.47, and r = −0.53 vs. r = −0.43, respectively). In addition, multiple regression analysis showed that parameters related to the BMIPP defect were also better predictive factors of EF both at the time of discharge and 90 days or more after the onset. In conclusion, resting123I-BMIPP and201Tl myocardial SPECT performed in the subacute phase of AMI were shown to be useful in predicting prognosis and ventricular function for patient management.

Clinical usefulness of iodine 123-labeled fatty acid imaging in patients with acute myocardial infarction

BackgroundIodine 123-labeled 15-(p-iodophenyl)-3R,S-methylpentadecanoic acid (BMIPP) has recently been developed, since normal myocardium metabolizes free fatty acids. This study investigated the clinical usefulness of BMIPP imaging in patients with acute myocardial infarction (MI), particularly in the detection of stunned myocardium in patients who underwent acute coronary revascularization.MethodsThe subjects were 41 patients with acute MI who had undergone emergency coronary revascularization. Both BMIPP and thallium-201 images at rest were obtained during the subacute phase. The myocardial distribution of radiotracers was quantified by generating circumferential count-distribution profile analysis. Initial 201 Tl imaging, delayed 201Tl imaging, and BMIPP imaging were performed, and the mean count densities in the infarct region (initial 201Tl images [TL1], delayed 201Tl images [TL2], and BMIPP images in the infarct region [BM], respectively) were obtained. The differences between mean count densities (TL1-BM: BM subtracted from TL1; TL2-BM: BM subtracted from TL2) were also calculated.ResultsBM showed a higher correlation with wall motion data by echocardiography (WM) in the acute phase than other nuclear imaging tests, whereas TL2 showed the highest correlation with WM in the chronic phase. Acute to chronic WM improvement showed a good correlation with TL2-BM.ConclusionSingle photon emission computed tomography imaging with BMIPP is a candidate for providing the “memory image” of ischemic damage, whereas TL2 reflects all viable tissue. The mismatch between the tracers can serve as an indicator of myocardial stunning.

Cilnidipine as an agent to lower blood pressure without sympathetic nervous activation as demonstrated by iodine-123 metaiodobenzylguanidine imaging in rat hearts.

Background: Administration of short-acting antihypertensive agents to patients with ischemic heart disease results in increased sympathetic nervous activity and is associated with worsened outcomes. Cilnidipine is an agent which blocks not only L-type calcium channels at the smooth muscle in the artery, but also N-type calcium channels at the presynaptic terminal. The goal of the present study was to determine the effect of cilnidipine on sympathetic nervous activity as on agent which blocks both L-type and N-type calcium channels at the presynaptic terminal, on sympathetic nervous activity in an experimental rat model using iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging.Methods: Fourteen-week-old Wistar-Kyoto rats were divided into 3 separate groups: CTR group (control: distilled water administered), Nif group (nifedipine administered), or Cil group (cilnidipine administered). Agents were administered via a stomach tube, followed by injection of MIBG via the femoral vein. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography just prior to administration of antihypertensive drugs and 150 minutes later. Initial imaging (Ce) and delayed imaging (Cd) were defined as the sum of density counts in the region of interest created by adjusting to myocardial edge, and were corrected for both physical decay and weight. The myocardial washout rate (WR) was defined as the percent change in the count density from the initial to delayed images.Results: Significant decreases in SBP were seen in the Nif group (from 132±3 mmHg to 85±5 mmHg, p<0.0001) and the Cil group (from 128±4 mmHg to 92±7 mmHg, p=0.0008), whereas no significant change in SBP was noted in the CTR group (from 123±5 mmHg to 127±3 mmHg). HR significantly increased in the Nif group (from 290±12/min to 378±14/min, p<0.0001) but not in the CTR (from 278±3/min to 300±6/min) or Cil (from 291±6/min to 303±5/min) groups. WR was significantly greater in the Nif group (64.7±0.5%) when compared to the CTR (56.4±1.2%, p=0.0031) or the Cil (55.4±2.2%, p=0.0016) groups.Conclusion: In contrast to nifedipine, administration of cilnidipine did not result in increased myocardial sympathetic nervous activation.

The relationship between clinical stage, prognosis and myocardial damage in patients with Duchenne-type muscular dystrophy: five-year follow-up study

The evaluation of myocardial damage by [123I] 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) imaging, which represents free fatty acid metabolism, has not been reported in patients with Duchenne-type muscular dystrophy (DMD). To date, the relationship between clinical stage, prognosis and myocardial damage has not been evaluated by radionuclear cardiac imaging. The main goal of this study was to elucidate the relationship of quantitative indices of myocardial damage obtained by radionuclear cardiac imaging ([201T1] and [123I] BMIPP) to clinical stage and incidence of severe cardiac events in patients with Duchenne-type muscular dystrophy (DMD).Methods: The study population consisted of 28 male patients with DMD. The average age at the beginning of observation was 19.1 ± 7.4 yrs. Nuclear tomographic imaging was performed using [201T1] and [123I] BMIPP. The mid-ventricular short axial slices were classified into four anatomical regions, and the normalized count data in these areas (TL, BM) were obtained. The endpoint was the occurrence of heart failure during the follow up period.Results: Thirteen cases of heart failure occurred during the 5-year follow-up period, including three cases with cardiac death due to congestive heart failure. Clinical staging correlated directly with TL (p = 0.0118) and BM (p = 0.0401) in the whole left ventricle. In regional TL analysis, an association was observed only in the septum (p = 0.0151), and in the anterior (p = 0.0361) region. The only discrepancy between the tracer parameters (TL — BM) in the septum was observed with the radionuclear cardiac values, which exhibited a relationship with cardiac events (p = 0.0124). This discordance, TL < BM, was contrary to that usually observed in patients with ischemic heart disease.Conclusion: The septum is the critical area of significance for cardiac events and outcome in patients with DMD. The uptake of [201T1] in this area was representative of the clinical stage, and TL-BM correlated well with the prognosis.

Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: A comparison of123I-MIBG scintigraphic and echocardiographic data

It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and123I-MIBG scintigraphy. Both of these methods are associated with β-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patients with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography; and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123 [123I] meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with123I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r=0.682, p=0.0146), wall motion after dobutamine stress (r=0.758, p=0.0043), the change in wall motion (r=0.667, p=0.0178), and with left ventricular diastolic diameter (r=0.837, p=0.0007). In addition, the123I-MIBG washout rate correlated with baseline wall motion (r=0.608, p=0.0360), wall motion after dobutamine stress (r=0.703, p=0.0107), and with the change in wall motion (r=0.664, p=0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure.

Detection of a coronary arterial thrombus by indium-111-oxine-labeled platelet scintigraphy

Coronary arteriography revealed significant left anterior descending coronary artery stenosis in a 72-year-old man with a history of myocardial infarction. Stenting of the stenotic vessel was performed. Twelve hours after stenting the patient complained of chest pain but emergent coronary arteriography did not show sign of any coronary arterial stenosis. Under suspicion of coronary thrombus formation, indium-111-oxine-labeled platelet scintigraphy was performed 5 days after stenting, and revealed accumulation of indium-111-oxine in the area corresponding to the stent implantation site.

Usefulness of indium-111-oxine-labeled leukocyte scintigraphy in diagnosis of inflammation associated with chronic aortic dissection

Background: Patients with chronic aortic dissection require monitoring for indications of disease progression. In present study, inflammation adjacent to associated aortic wall was evaluated by indium-111-oxine-labeled leukocyte scintigraphy, scince inflammation of the blood vessel wall often associates with progression of chronic aortic dissection.Methods and Results: Fifteen patients with aortic dissection underwent indium-111-oxine-labeled leukocyte scintigraphy. Seven showed positive images at sites corresponding to the actual sites of the dissociated aorta. Four patients with positive images underwent surgery. Histologic examination revealed inflammatory and necrotic changes of the aortic wall. During a mean follow-up period of 2.3 years, progression of aortic dissection was observed in two of the seven patients with positive intimal imaging.Conclusion: Indium-111-oxine-labeled leukocyte scintigraphy may be a useful noninvasive technique to assess the persistent inflammation in patients with chronic aortic dissection.

Mechanisms Responsible for Delayed and Immediate Hemolytic Transfusion Reactions in a Patient with Anti‐E + Jkb + Dib and Anti‐HLA Alloantibodies

Immediate hemolytic transfusion reactions (IHTR) occurred in the course of delayed hemolytic transfusion reactions (DHTR).An 84‐year‐old man had received a blood transfusion 20 years ago. Progressive anemia developed, because of continuous bleeding from a bladder tumor. He was transfused with concentrated red blood cells (CRC) which were Rh‐E antigen negative, because he had anti‐E antibodies (day 0). He received CRC on day 3, and underwent resection of bladder tumor on day 6. Although crossmatch‐compatible CRCs were prepared for the operation, those were not required and were kept in a refrigerator in the ward. On day 9, when a CRC kept in the ward was transfused, he suddenly had a IHTR. In order to analyze a mechanism of IHTR, the anti‐Jkb and anti‐Dib antibodies, anti‐HLA antibodies and the concentrations of inflammatory cytokines were measured in serum samples. The anti‐Jkb and anti‐Dib antibodies increased prior to IHTR experienced on day 9. The concentrations of IL‐6 and IL‐1β increased from day 2, while the concentration of IL‐8 increased from day 7. The anti‐HLA class I antibody could be detected 2 days before IHTR. Thus, the anti‐Jkb and anti‐Dib antibodies induced the production of inflammatory cytokines and symptoms of DHTR and IHTR. The anti‐HLA class I antibody could be produced in spite of using the filer for removing leukocytes, and may take part in the induction of IHTR. Further, blood products should be transfused soon after completing a crossmatch test in patients with anti‐RBC alloantibodies.

Comparative accuracy of various Tl-201 reinjection imaging protocols to detect myocardial viability

The conventional exercise-3 hours-redistribution thallium-201 [201Tl] imaging protocol has been recognized to be suboptimal for reliable detection of myocardial viability. Although201Tl restreinjection after exercise has improved detection of viable myocardium, it is still underestimated in some patients. The present study was designed to compare detection of viable myocardium in five separate imaging steps: step 1: initial-exercise imaging, step 2: delayed-exercise imaging, step 3: Tl-201 reinjection imaging after delayed-exercise imaging, step 4: separate day rest-reinjection imaging, and step 5: separate day delayed-rest imaging. The study group consisted of 22 patients scheduled for coronary revascularization (either percutaneous transluminal coronary angioplasty or coronary bypass surgery). Pre- and postintervention echocardiographic wall motion and thickness served as independent markers of myocardial viability. Results: Accuracy in identifying myocardial viability gradually improved incrementally from201Tl imaging step 1 to step 5. The positive predictive value, negative predictive value and overall accuracy were best for the separate day delayed-rest study (step 5) at 90%, 33% and 78%, respectively. Myocardial segments had fixed defects on separate day delayed-rest201Tl imaging (step 5), but nevertheless echocardiographic evidence of myocardial viability indicated less severe defects than segments judged non viable by echocardiography (p = 0.021). The overall accuracy of separate day delayed-rest imaging (step 5) in predicting viability improved to 88% when segments with moderate or mild defects were considered viable. In conclusion, the most reliable predictor of myocardial viability with201Tl imaging is defect severity on separate day delayed-rest images.