Cortical circumferential profile of SPECT cerebral perfusion in Alzheimer''s disease

We developed a semiautomatic method termed “cortical circumferential profiling” for objective analysis of cerebral cortex function in emission tomographic neuroimaging studies. This method treats cortex as a continuous ring near the outer brain edge. A computer algorithm samples the cortex at 60 contiguous, equiangular locations, using 1-cm² samples. These values are plotted as a function of cortical angle to produce the cortical circumferential profile. This method was used in a study of regional cerebral perfusion in 15 patients with Alzheimer's disease and 8 elderly control subjects using N-isopropyl [I-123]-iodoamphetamine. Cortical circumferential profiling decreases variability, examines the entire cortex within slices at preselected levels above the orbital-meatal line, and facilitates intrasubject and intersubject comparisons.     

肺灌注显像在Ⅲ期非小细胞肺癌调强放疗中对功能肺的保护

目的 探讨肺灌注显像在Ⅲ期非小细胞肺癌(NSCLC)调强放疗(IMRT)保护功能肺的可行性。方法 选择拟行放疗的Ⅲ期NSCLC患者24例,分别行PET-CT和SPECT定位,图像传至治疗计划系统进行图像融合。根据SPECT图像确定功能肺(FL)和非功能肺(NFL),FL是指放射性计数为最大放射性计数的30%以上(包括30%)的区域,其他区域为NFL。肺灌注受损分为4级:0级,无灌注受损;1级,肿瘤及其周围局部肺灌注受损;2级,达1叶肺灌注受损;3级,超过1叶肺灌注受损。根据SPECT图像提供的肺功能信息制定IMRT计划进行优化,尽可能降低FL的照射体积剂量。采用配对t检验统计分析优化前后的IMRT计划的肺组织剂量参数变化。结果 患者均有不同程度的肺灌注缺损,其中肺灌注受损1级8例,2级6例,3级10例。根据SPECT提供的肺功能信息优化IMRT计划后WLV和FLV均有不同程度降低,而FLV降低程度更加明显。优化后WLV₁₀、WLV₁₅、WLV₂₀、WLV₂₅、WLV₃₀和FLV₁₀、FLV₁₅、FLV₂₀、FLV₂₅、FLV₃₀差异有统计学意义。结论 根据SPECT图像提供的肺功能信息优化IMRT计划以保护Ⅲ期NSCLC功能肺是可行的。     

Evaluation of left ventricular mechanical dyssynchrony as determined by phase analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left ventricular dysfunction and conduction disturbances

Background  Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms. Methods and Results  A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P=.001). Conclusions  A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in the evaluation of patients for CRT. This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the primary investigator.     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

Interobserver and interstudy variability of myocardial blood flow and flow-reserve measurements with nitrogen 13 ammonia-labeled positron emission tomography

Background  

Experimental studies have shown that positron emission tomography (PET) with ¹³N-labeled ammonia provides accurate quantification of regional myocardial blood flow (MBF) under rest and stress conditions. To establish the clinical utility of this method, the interobserver variability and the temporal variability of serial measurements of blood flow and coronary flow reserve (CFR) must be known. This study investigated the interobserver and temporal reproducibility of ¹³N-labeled PET for measurement of MBF and CFR.     

Application of technetium-99m hexamethylpropylene amine oxime single-photon emission tomography to neurologic prognosis in patients undergoing urgent carotid surgery

In this study we aimed to work out a quantitative prognostic index for preoperative assessment of brain technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET) in patients referred for urgent carotid endarterectomy due to acute obstructive disease of the internal carotid artery (ICA) and neurological deficit. To this end we compared data from preoperative SPET studies with the postinterventional changes in neurological status in 20 patients (17 males, three females; mean age 53 years, SD 4 years) with acute ischaemic cerebral disorders induced by obstruction of the ICA. Carotid obstruction was diagnosed by ultrasound B-mode study. All patients underwent urgent carotid endarterectomy from the ICA. Patients were divided into two groups in accordance with the results of postoperative follow-up: group A comprised patients with significant (more than 3 points) postoperative improvement in neurological condition as quantified by the Canadian Neurological Scale (11 patients); group B consisted of patients with minimal improvement or deterioration (nine, three of whom died). All patients were studied preoperatively by^99mTc-HMPAO SPET. The volume of nonperfused tissue (VS, cm³) was quantified using the Mountz technique. Hypoperfused volume (V _hypoperf, cm³) in the affected hemisphere was calculated as the total volume of voxels with^99mTc-HMPAO uptake <90% of the contralateral symmetric voxels. Discriminant prognostic function was calculated by discriminant analysis as:PF = 0.072×VS + 29.46×(VS/V _hypoperf). Patients with preoperativePF values <8.20 demonstrated postoperative improvement in neurological status, while the group withPF>8.90 comprised patients who demonstrated minimal improvement or deterioration. PF values in the range 8.20–8.90 carried an indefinite prognosis. We conclude that the preoperative^99mTc-HMPAO SPET can be used for the selection of patients in whom improvement in neurological status may be expected after urgent surgical correction of acute extracranial obstruction of the ICA.     

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

乌拉坦对大鼠肾脏滤过功能的影响

以９９ｍＴｃ－ＤＴＰＡ颈静脉“弹丸”式注入，用ＳＰＥＣＴ技术研究乌拉坦麻醉大鼠的肾脏滤过功能。结果表明乌拉坦麻醉大鼠肾脏滤过功能明显降低（Ｐ＜０．０５），与给药途径无关。     

Mechanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent

Background BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. Methods and Results Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC₅₀ of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC₅₀ of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%) and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC₅₀ value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t_1/2) uptake was very rapid (approximately 35 seconds), and washout t_1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. Conclusions F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.