Single-photon Emission Computed Tomography Analysis Research Articles

Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study

Multidrug resistance (MDR) has been suggested to be a major cause of failure of chemotherapy treatment for cancer. It is associated with the expression of MDR-related and apoptosis-related proteins. Recently, technetium-99m hexakis 2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR. The aim of this study was to evaluate (99m)Tc-MIBI single-photon emission computed tomography (SPECT)(/CT) for functional imaging of MDR-related and apoptosis-related proteins in patients with ovarian cancer. Eleven women (mean age 63 years, range 53-76) with a clinical suspicion of ovarian cancer were prospectively studied. All patients were examined with (99m)Tc-MIBI imaging before surgery. After intravenous injection of 740 MBq (99m)Tc-MIBI, SPECT(/CT) imaging at 10 min and 2 h was performed. Based on the semiquantitative analysis of (99m)Tc-MIBI SPECT(/CT), both early and delayed tumor uptake ratios and washout rate % were calculated. The expression of MDR-related and apoptosis-related proteins was assessed in surgically excised tumors. Immunohistochemical staining was performed to quantify the expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein1 (MRP1), MRP3, lung resistance protein (LRP), breast cancer resistance protein (BCRP), Y-box-binding protein-1 (YB-1), Bcl-2, Bax and glutathione-S-transferase. (99m)Tc-MIBI imaging results and immunohistochemical results were compared. Laparotomy was performed in all patients. Six ovarian cancers were proven by histopathological examination. Five of the six ovarian cancers were positive for (99m)Tc-MIBI uptake on both early and delayed images with (99m)Tc-MIBI SPECT(/CT). MDR-related and apoptosis-related proteins were found to be expressed in all tumors. For the five positive (99m)Tc-MIBI uptake cases, the washout rate % of (99m)Tc-MIBI uptake showed a significant positive correlation with the expression of YB-1 (r = 0.988, P = 0.0015), and the early tumor uptake ratio showed a significant positive correlation with the expression of Bax (r = 0.882, P = 0.047). Our results suggested that (99m)Tc-MIBI SPECT(/CT) might be a valuable diagnostic imaging technique to evaluate MDR-associated YB-1 and Bax-mediated apoptosis in patients with ovarian cancer.

Combined Balloon Test Occlusion and SPECT Analysis for Carotid Sacrifice: Angiographic Predictors for Success or Failure?

Objectives To evaluate angiographic patterns that may predict the success or failure of carotid artery balloon test occlusion (BTO) and single-photon emission computed tomography (SPECT) analysis for carotid sacrifice. Study Design This is a retrospective nonrandomized study. Study Setting Conducted at the University of California Davis Medical Center, Sacramento, California. Patients A total of 31 patients, ranging from 24 to 83 years of age, with a mean age of 61 years (22 men, 9 women) with head and neck cancer (26 patients), malignant glomus tumor (1 patient) or giant carotid aneurysms (4 patients) as possible candidates for surgical carotid artery sacrifice were evaluated from September 2005 to September 2012. Methods All patients underwent unilateral internal carotid artery balloon test occlusion with SPECT analysis (20 mCi technetium 99m-hexamethyl propyleneamine oxime [HMPAO]) imaging before and during carotid occlusion. Carotid angiography with carotid cross-compression (manual compression of the cervical artery contralateral to the side of contrast injection) was used to analyze filling through the anterior communicating artery to the contralateral hemisphere. Intervention The balloon occlusion was terminated in two patients because of deterioration of the neurologic exam. Main Outcome Measures All patients who passed the neurologic examination during BTO and also passed the SPECT occlusive study underwent successful carotid sacrifice without neurologic sequelae. Patients failing the occlusive neurologic examination and/or the SPECT study elected chemoradiation, with the exception of one patient who underwent a successful carotid bypass graft and carotid resection. Results The success of carotid sacrifice in patients passing both the occlusive test and the SPECT analysis for carotid sacrifice was 100%. Three patients failed both the BTO and the SPECT, with two demonstrating no anterior circulation cross-fill, but one showed some cross-fill. Six additional patients passed the BTO but failed the SPECT, with poor cross-fill in five patients. In addition, three patients who had excellent cross-fill through the anterior communicating artery to the contralateral hemisphere failed the SPECT examination in two cases and failed both tests in another case.

Development of Digital Myocardial Phantom to Evaluate Software for Gated SPECT

Background: Real cardiac phantoms are often used to assess the performance of software for gated single-photon emission computed tomography(SPECT) . However, these phantoms have disadvan- tages in that they are not very similar to actual hearts and setting a perfusion defect is not easy. To overcome these problems, we developed a digital myocardial phantom, named%Myo-Simu' . The aims of this study were to check its operation when being incorporated into gated SPECT software and to elucidate its usefulness to assess properties of software. Methods: Myo-Simu yields a simulated left ventricle(LV)approximated as a moving spheroid that preserves shape similarity during the cardiac cycle with a fixed total myocardial volume. Wall thickness, background activity, spatial resolution, statistical noise, and perfusion defects are incorporated into the phantom, and these conditions can be modified by changing the input parameters. We generated various types of hearts by changing the length of the short and long axes, patterns of perfusion defects, spatial resolution, and image noise. Generated SPECT images were applied to Quantitative Gated SPECT(QGS) , Heart Function View, and EXINI Heart software to check the adaptability to gated SPECT analyses. We also evaluated the influences of wall thickness and spatial resolution on QGS analyses. Results: Myo-Simu successfully generated SPECT images of various geometries. These images can be applied to gated SPECT analyses without any problems in operation. In QGS, measured LV volumes changed greatly depending on wall thickness and spatial resolution. Conclusions: Myo-Simu is a feasible phantom for assessing gated SPECT software.

The utility of cerebral perfusion SPECT analysis using SPM8, eZIS and vbSEE for the diagnosis of multiple system atrophy-parkinsonism.

Although a correct diagnosis is important for appropriate management, accurately differentiating between multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) is often difficult because of similarities in the early-stage symptoms. The aim of this study was to evaluate the diagnostic value of cerebral perfusion single photon emission computed tomography (SPECT) and voxel-based analysis for diagnosing MSA-P patients. Thirty-eight subjects (9 with early-stage MSA-P, 11 with PD, and 18 controls) were included in this study. Z-scores suggestive of hypoperfusion were calculated between patients and controls using statistical parametric mapping (SPM) 8 and easy Z-score imaging system (eZIS) programs. A voxel-based stereotactic extraction estimation (vbSEE) program was performed to determine the target volumes of interest (VOIs) in the putamen, pons, and cerebellum, and quantify Z-scores as "extent" (the rate of voxels with a Z-score >2.0 in these VOIs) and "severity" (average Z-scores in these VOIs). These parameters were used as the determinant in receiver operating characteristic (ROC) analyses. The extent and severity of the cerebellar VOIs were higher in MSA-P patients than in PD patients. In ROC analyses, the extent and severity of the cerebellar VOI exhibited the highest areas under the curves of 0.86 and 0.84, and accuracies of 90 and 90 %, respectively. The diagnostic value of significant cerebellar hypoperfusion was the highest for differentiating MSA-P from PD. This voxel-based analysis of cerebral perfusion SPECT using the SPM8, eZIS, and vbSEE programs is useful for clinically diagnosing MSA-P.

Brain SPECT can differentiate between essential tremor and early-stage tremor-dominant Parkinson’s disease

There are no confirmatory or diagnostic tests or tools to differentiate between essential tremor (ET) and tremor in idiopathic Parkinson’s disease (PD). Although a number of imaging studies have indicated that there are differences between ET and PD, the functional imaging study findings are controversial. Therefore, we analyzed regional cerebral blood flow (CBF) by perfusion brain single-photon emission computed tomography (SPECT) to identify differences between ET and tremor-dominant Parkinson’s disease (TPD). We recruited 33 patients with TPD, 16 patients with ET, and 33 healthy controls. We compared the severity of tremor symptoms by comparing the Fahn-Tolosa-Marin rating scale (FTM) score and the tremor score from Unified Parkinson’s Disease Rating Scale (UPDRS) between TPD and ET patients. Subjects were evaluated by neuropsychological assessments, MRI and perfusion SPECT of the brain. Total FTM score was significantly higher in ET patients than TPD patients. However, there was no significant difference in FTM Part A scores between the two patient groups, while the scores for FTM Part B and C were significantly higher in ET patients than TPD patients. Brain SPECT analysis of the TPD group demonstrated significant hypoperfusion of both the lentiform nucleus and thalamus compared to the ET group. Brain perfusion SPECT may be a useful clinical method to differentiate between TPD and ET even during early-phase PD, because the lentiform nucleus and thalamus show differences in regional perfusion between these two groups during this time period. Additionally, we found evidence of cerebellar dysfunction in both TPT and ET.

SPECT Analysis of Cardiac Perfusion Changes After Whole-Breast/Chest Wall Radiation Therapy With or Without Active Breathing Coordinator: Results of a Randomized Phase 3 Trial

Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before and 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segment's perfusion. Scores were analyzed with nonparametric tests and linear regression. Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.

Validation of automated quantification of myocardial perfusion single-photon emission computed tomography using Heart Score View in patients with known or suspected coronary artery disease.

Heart Score View (HSV) is a free software package for automated quantification of myocardial single photon emission computed tomography (SPECT) imaging using a standard Windows computer. We compared scoring results of myocardial perfusion among visual analysis, Quantitative Perfusion SPECT (QPS), and HSV in patients with known or suspected coronary artery disease.This study included 75 consecutive patients with known or suspected coronary artery disease who underwent adenosive stress-rest Tl-201 SPECT. Analysis of myocardial perfusion SPECT was performed on a standard 17-segment model visually and using QPS and HSV.There were 54 male and 21 female patients with a mean age of 70.5 ± 10.7 years. Thirteen patients (17%) had prior myocardial infarction. Summed stress score (SSS) and summed rest score (SRS) in the mid and basal areas were significantly higher on HSV than visual analysis or QPS. There was no significant difference in SDS in the whole area among the 3 methods. Similar results were found even in patients without prior myocardial infarction. Manual setting of the left ventricular cavity improved the correlations of SSS, SRS and SDS between HSV and the other methods.Our data suggested that HSV was comparable with visual analysis or QPS in scoring myocardial perfusion when manual setting of the left ventricular cavity is applied.

Global scaling for semi-quantitative analysis in FP-CIT SPECT.

Semi-quantitative characterization of dopamine transporter availability from single photon emission computed tomography (SPECT) with 123I-ioflupane (FP-CIT) is based on uptake ratios relative to a reference region. The aim of this study was to evaluate the whole brain as reference region for semi-quantitative analysis of FP-CIT SPECT. The rationale was that this might reduce statistical noise associated with the estimation of non-displaceable FP-CIT uptake. 150 FP-CIT SPECTs were categorized as neurodegenerative or non-neurodegenerative by an expert. Semi-quantitative analysis of specific binding ratios (SBR) was performed with a custom-made tool based on the Statistical Parametric Mapping software package using predefined regions of interest (ROIs) in the anatomical space of the Montreal Neurological Institute. The following reference regions were compared: predefined ROIs for frontal and occipital lobe and whole brain (without striata, thalamus and brainstem). Tracer uptake in the reference region was characterized by the mean, median or 75th percentile of its voxel intensities. The area (AUC) under the receiver operating characteristic curve was used as performance measure. The highest AUC of 0.973 was achieved by the SBR of the putamen with the 75th percentile in the whole brain as reference. The lowest AUC for the putamen SBR of 0.937 was obtained with the mean in the frontal lobe as reference. We recommend the 75th percentile in the whole brain as reference for semi-quantitative analysis in FP-CIT SPECT. This combination provided the best agreement of the semi-quantitative analysis with visual evaluation of the SPECT images by an expert and, therefore, is appropriate to support less experienced physicians.

Cortical hemichorea–hemiballism

Hemichorea-hemiballism (HCHB) was infrequently related to cortical lesions such as tumor or infarction. Although functional derangement of the basal ganglia (BG) or the thalamus (Th) was suggested, pathomechanism of HCHB secondary to cortical lesions remains uncertain. We recruited the patients with HCHB secondary to cerebrovascular diseases, excluding other causes such as hyperglycemia. All the patients were studied with brain magnetic resonance imaging/angiography (MRI/MRA) and single-photon emission computed tomography (SPECT). Those with only cortical abnormalities in neuroimaging studies were sorted out as the cases of cortical HCHB. Statistical parametric mapping (SPM) analysis of SPECT was performed to investigate the pathomechanism of cortical HCHB. Ten patients (three males and seven females) were included in our study. Six patients had acute BG lesions with SPECT abnormalities, and one had old BG lesions with abnormal SPECT. Three patients were classified as cortical HCHB with lesions only in the frontal and parietal cortices in MRI and SPECT. SPM analysis revealed additional hypoperfusion in frontal areas, leaving BG and Th free of any perfusion abnormalities. Although cortical HCHB was strictly defined by MRI and SPECT, cortical HCHB was not uncommon (30 %). Further analysis showed intertwined networks among the frontal and parietal lobes for cortical HCHB. Cortical dysfunction is important in the pathogenesis of cortical HCHB even without significant involvement of BG and Th.

Perfusión y función ventricular en SPECT cardiaco y coronariografía del mismo día según localización en enfermedad de un vaso

Single-photon emission computed tomography (SPECT) can be used as a non-invasive tool for the assessment of coronary perfusion. To assess ventricular perfusion and function by SPECT in patients with single vessel coronary artery disease. Among patients with indications for a coronary artery angiography, those with significant lesions in one vessel, were selected for the study. Within 24 hours, cardiac SPECT examinations on basal conditions and after high doses of dipyridamole, were performed. SPECT data from 38 patients with a low probability of coronary artery disease was used for comparisons. Ten patients aged 61 ± 8 years (seven men) were studied. Visual analysis of SPECT revealed signs suggestive of ischemia in eight patients. The remaining two patients did not have perfusion disturbances. SPECT detected eight of ten abnormal vessels reported in the coronary artery angiography. There were two false negative results Summed stress, summed rest and summed difference scores were 9.78 ± 6.51, 3.22 ± 5.07 and 6.33 ± 4.97, respectively. The ejection fractions under stress and at rest were 53 ± 11.7% and 61 ± 15.7% respectively (p < 0.01). The figures for the control group were 69.1 ± 13.5% and 75.2 ± 12.04% respectively (significantly different from patients). Two patients had a summed motion score above 14.9. Likewise, two patients had a summed thickening score above 10.9. SPECT detected 80% of coronary lesions found during coronary artery angiography. Visual analysis of perfusion is highly reliable for diagnosis. Quantitative parameters must be considered only as reference parameters.

Combination of pretest probability and high sensitivity cardiac Troponin I and T in the detection of exercise-induced myocardial ischemia

Purpose: In order to provide incremental value for clinical practice, new biomarkers need to improve accuracy on top of pretest probability. The aim of this study was to prospectively quantify pretest probability in patients with suspected exercise-induced myocardial ischemia and to evaluate, whether novel high sensitivity cardiac Troponin (hs-cTn) assays provide incremental diagnostic information. Methods: We enrolled a total of 274 consecutive patients with suspected myocardial ischemia referred for ergometer myocardial perfusion single-photon emission computed tomography (SPECT). Pretest probabilities for myocardial ischemia were quantified by the treating cardiologist using a visual analogue scale before and after exercise testing blinded to SPECT analysis and the measurement of hs-cTn. Hs-cTnI (Abbott) and hs-cTnT (Roche) were measured before exercise testing. Patients with missing laboratory measurements of hs-TnI were excluded from analysis (n = 49), leaving a total of 225 patients with both measurements. Result: Exercise-induced myocardial ischemia was detected in 114 (41.6%) of patients. The area under the ROC curve (AUC) for pretest probability after exercise testing alone was 0.7. The AUC for pretest probability with hs-TnI and with hs-TnT was 0.725 and 0.755, respectively. (p = 0.064). Both, pretest probability with hs-cTnI (p = 0.014 for comparison) and pretest probability with hs-cTnT (p = 0.006 for comparison), had significantly higher AUCs than pretest probability alone. ![Figure][1] AUC of pretest probability, hsTnI, hsTnT Conclusions: Measurement of hs-TnI and hs-TnT, respectively, before exercise-testing improves the diagnostic performance of clinical judgment for myocardial ischemia. It could help in clinical decision making in patients with suspected myocardial ischemia. [1]: pending:yes

The relationship between the diagnosis method of neuronal dysfunction (DIMENSION) and brain pathology in the early stages of Alzheimer's disease

To examine whether the diagnosis method of neuronal dysfunction (DIMENSION), a new electroencephalogram (EEG) analysis method, reflected pathological changes in the early stages of Alzheimer's disease (AD), we conducted a comparative study of cerebrospinal fluid markers and single-photon emission computed tomography. Subjects cincluded 32 patients in the early stages of AD with a Mini-Mental State Examination score ≥24 (14 men, 18 women; mean age, 77.3 ± 9.2 years). Cerebrospinal fluid samples were collected from AD patients, and cerebrospinal fluid levels of phosphorylated tau protein (p-tau) 181 and amyloid β (Aβ) 42 were measured with sandwich ELISA. EEG recordings were performed for 5 min with the subjects awake in a resting state with their eyes closed. Then, the mean value of the EEG alpha dipolarity (Dα) and the standard deviation of the EEG alpha dipolarity (Dσ) were calculated with DIMENSION. Single-photon emission computed tomography analyses were also performed for comparison with DIMENSION measures. Patients with parietal hypoperfusion had significantly increasing p-tau181, decreasing Dα, and increasing Dσ. In addition, there was a negative correlation between Dα and p-tau181, p-tau181/Aβ42, and a positive correlation between Dσ and p-tau181/Aβ42. Dα and Dσ were related to cerebral hypoperfusion and p-tau181/Aβ42. DIMENSION was able to detect changes in the early-stage Alzheimer's brain, suggesting that it is possibility as a useful examination for early-stage AD with a difficult discrimination in clinical conditions. Moreover, EEG measurement is a quick and easy diagnostic test and is useful for repeated examinations.

Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy

The use of adipose mesenchymal stromal cells (ASCs) in cellular and genic therapy has attracted considerable attention as a possible treatment for neurodegenerative disorders, including Parkinson disease. However, the effects of gene therapy combined with intracerebral cell transplantation have not been well defined. Recent studies have demonstrated the respective roles of LIM homeobox transcription factor 1, alpha (LMX1A) and Neurturin (NTN) in the commitment of embryonic stem cells (ESCs) to a midbrain dopaminergic neuronal fate and the commitment of mesenchymal stromal cells to cells supporting the nutrition and protection of neurons. We investigated a novel in vitro neuronal differentiation strategy with the use of LMX1A and Neurturin. We were able to elicit a neural phenotype regarding cell morphology, specific gene/protein expression and physiological function. Neuronal-primed ASCs derived from rhesus monkey (rASCs) combined with adenovirus containing NTN and tyrosine hydroxylase (TH) (Ad-NTN-TH) were implanted into the striatum and substantia nigra of methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored with the use of behavioral tests and health measures until the fourth month after implantation. The differentiated cells transcribed and expressed a variety of dopaminergic neuron-specific genes involved in the SHH/LMX1A pathway. Single-photon emission computed tomography analysis and postmortem analysis revealed that the grafting of rASCs combined with Ad-NTN-TH had neuroprotective effects compared with Ad-NTN-TH or rASCs alone. Behavioral measures demonstrated autograft survival and symptom amelioration. These findings may lead to cellular sources for autologous transplantation of Parkinson disease. Combined transplantation of Ad-NTN-TH and induced rASCs expressing LMX1A and NTN may be a better therapy candidate for the treatment of Parkinson disease.

Quantitative evaluation of crossed cerebellar diaschisis, using voxel-based analysis of Tc-99m ECD brain SPECT

In the recent literature there is no consensus regarding the relationships between crossed cerebellar diaschisis (CCD) with the primary lesion size, severity or location. Thus, the aim of the present study was to investigate relationship between the size and severity of cerebral lesions and CCD in patients with chronic stroke, using voxel-based analysis of Tc-99m ECD single-photon emission computed tomography (SPECT). We retrospectively reviewed data of 57 patients with chronic ischemic lesions localized unilaterally in the cerebral hemisphere. SPECT evaluation was performed with the voxel-based analysis. The percentage inter-hemispheric asymmetry index (AI) and the volume of abnormal clusters of voxels (CV) were ascertained for hypoperfusion in the supratentorial lesion and contralateral cerebellum. CCD was present in 35.1% cases. In Group CCD (+), the CV and AI of supratentorial hypoperfusion (median 128.1 ml and 21.9%, respectively) were significantly higher compared with Group CCD(-) (median 41.4 ml and 18.0%, respectively). Statistically significant correlation was found between CV of supratentorial and cerebellar perfusion defects (r = 0.4; p < 0.05), between AI of supratentorial and cerebellar perfusion defects (r = 0.6; p < 0.05) and between CV of supratentorial defect and AI of cerebellar perfusion defects (r = 0.6; p < 0.05). Our data suggest, that in the chronic stage of stroke, the size and severity of the supratentorial lesion are determinants of CCD, correlating with the degree of cerebellar hypoperfusion.

Incremental diagnostic accuracy of hybrid SPECT/CT coronary angiography in a population with an intermediate to high pre-test likelihood of coronary artery disease

Hybrid myocardial perfusion imaging with single photon emission computed tomography (SPECT) and CT coronary angiography (CCTA) has the potential to play a major role in patients with non-conclusive SPECT or CCTA results. We evaluated the performance of hybrid SPECT/CCTA vs. standalone SPECT and CCTA for the diagnosis of significant coronary artery disease (CAD) in patients with an intermediate to high pre-test likelihood of CAD. In total, 98 patients (mean age 62.5 ± 10.1 years, 68.4% male) with stable anginal complaints and a median pre-test likelihood of 87% (range 22-95%) were prospectively included in this study. Hybrid SPECT/CCTA was performed prior to conventional coronary angiography (CA) including fractional flow reserve (FFR) measurements. Hybrid analysis was performed by combined interpretation of SPECT and CCTA images. The sensitivity, specificity, positive (PPV), and negative (NPV) predictive values were calculated for standalone SPECT, CCTA, and hybrid SPECT/CCTA on per patient level, using an FFR <0.80 as a reference for significant CAD. Significant CAD was demonstrated in 56 patients (57.9%). Non-conclusive SPECT or CCTA results were found in 32 (32.7%) patients. SPECT had a sensitivity of 93%, specificity 79%, PPV 85%, and NPV 89%. CCTA had a sensitivity of 98%, specificity 62%, PPV 77%, and NPV 96%. Hybrid analysis of SPECT and CCTA improved the overall performance: sensitivity, specificity, PPV, and NPV for the presence of significant CAD to 96, 95, 96, and 95%, respectively. In > 40% of the patients with a high pre-test likelihood no significant CAD was demonstrated, emphasizing the value of accurate pre-treatment cardiovascular imaging. Hybrid SPECT/CCTA was able to accurately diagnose and exclude significant CAD surpassing standalone myocardial SPECT and CCTA, vs. a reference standard of FFR measurements.

&lt;sup&gt;201&lt;/sup&gt;Tl心筋SPECTにおける三次元動画表示を用いた左室壁運動評価の検討─心臓CTとの比較─

Advances in computed tomography (CT) technology make it possible to obtain left ventricular wall motion using 3D reconstruction. In this study, we compared the images obtained from CT and (201)Tl electrocardiogram (ECG) gated single photon emission computed tomography (SPECT). In 20 patients with ischemic heart disease, we performed (201)Tl ECG gated SPECT (GE Healthcare Millennium VG) and ECG gated CT (Philips Medical Systems Brilliance iCT) to evaluate of left ventricular wall motion during the resting phase. In SPECT, left ventricular images were reconstructed using quantitative gated SPECT (QGS) software. In CT, the images were reconstructed using Virtual Place (AZE Software). The left ventricle was classified into five regions (anterior, lateral, inferior, septal, and apical). The amplitude of the wall motion was classified into five grades according to AHA classification. The values of the wall motion were separately checked by two radiographers. Assessment of left ventricular function myocardial wall movement using the three-dimensional movie display with ECG gated myocardial SPECT data was in agreement with the evaluation by cardiac CT inspection, and corresponded with wall motion in 88 of all 100 segments. SPECT analysis has the same quantity as that of obtained from CT for evaluation of left ventricular wall motion.

Visual and quantitative perfusion analysis in left main stem disease: a CE-MARC substudy

Background Left main stem (LMS) disease occurs in approximately 5% of patients with stable angina. It confers adverse prognosis, with potential for prognostic gain with revascularization. Single-photon emission computed tomography (SPECT) and CMR fail to detect ischemia in 41% and 18% of patients with significant LMS stenosis respectively [1], likely in part because of balanced reduction in coronary perfusion. It is not known whether quantitative assessment of myocardial blood flow (MBF) can improve diagnostic rates. The CE-MARC study prospectively enrolled 752 patients with suspected coronary artery disease, scheduled to undergo CMR, SPECT and X-ray coronary angiography [2]. We assessed the diagnostic performance of visual and quantitative perfusion CMR in CE-MARC patients with LMS disease. Methods All patients from the CE-MARC population with LMS disease ≥50%, or LMS equivalent disease (proximal LAD and proximal LCx ≥70%) on quantitative angiography were studied. A control group (matched for age and gender, excluding LMS or 3-vessel disease) was randomly selected from the CE-MARC population. Visual SPECT and CMR analyses were from the original, blinded read of CE-MARC. Only perfusion components of the CE-MARC CMR and SPECT protocols were analyzed. MBF was calculated offline (PMI v0.4) using the Fermi model from CMR stress perfusion images, with arterial input defined in LV blood pool, and LAD and LCx segments in the mid-LV short axis myocardial slice as tissue response. Results

Emerging Applications of an Experimental Single Photon Emission Computed Tomography: An Analysis of 16 Areas of Interest in the Pig’s Model

This paper aims to affirm various new applications of single photon emission computed tomography (SPECT) technique by utilizing the pig's models. Evaluation and subsequent analysis of SPECT results was conducted on the jaws of eight experimental pigs with a total of 16 areas of interest. The various reasons for which each experiment was conducted were evaluated and these reasons include: i) validation of a new bone grafting technique for closure of oro-antral communications, ii) comparison of autogeneous bone graft with other bone grafts, iii) sequential confirmation of osteoblastic activity of the sandwich bone regeneration technique with another technique, iv) validation of the use of a new membrane for guided tissue regeneration (GTR), v) validation of the fact that osseointegration is better with beaded implants than with threaded implants, and vi) validation of the fact that GTR is essential for immediate implant practice. The outcome of this evaluation is critically analysed against the background of the substantial clinical evidence where applicable, so as to appreciate the position of SPECT Following the evaluation of 16 areas of interest in eight experimental pigs, it was shown that experimental SPECT was valuable in the validation of the above reasons. It appears to be a modality that can continuously be utilized to validate and compare situations which would display osteoblastic activities. It is concluded that the bone scintigraphy imaging technique accurately reflects osteoblastic activities and can now be used to validate osseointegration of any implant or bone-grafting system. This can be done in conjunction with histological and histomorphometic analysis and such results obtained from SPECT should be correlated with the histological and histomorphometric analysis if available.

Hepatoprotective effect and mechanistic insights of deoxyelephantopin, a phyto-sesquiterpene lactone, against fulminant hepatitis

Deoxyelephantopin (DET) is an abundant sesquiterpene lactone isolated from an anecdotally hepatoprotective phytomedicine, Elephantopus scaber. Our objective in this study was to provide scientific evidence for the in vivo efficacy and the underlying mechanisms of action of DET in lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced fulminant hepatitis. We investigated both the protective effect of pretreatment with DET (10 mg/kg body weight, Pre-DET10) prior to administration of LPS/D-GalN and the therapeutic effect of treatment with 10 mg/kg DET (Post-DET10) or the hepatoprotective drug silymarin (Post-SM10) following the administration of LPS/D-GalN. Our data showed that Pre-DET10 prevented LPS/D-GalN-induced infiltration of F4/80 monocytes/macrophages and an increase of nitrotyrosine and cyclooxygenase-2 protein in liver tissues. Further, Post-DET10 and Psot-SM10 treatments protected against liver cell apoptosis. All three treatments suppressed serum aminotransferase activities, tumor necrosis factor-alpha and interleukin-6 levels, and serum and hepatic matrix metalloproteinase-9 activity. The Pre-DET10 or Post-DET10 and Post-SM10 treatments in combination with inhibition of heme oxygenase-1 expression ultimately decreased protection of mice from LPS/D-GalN-induced mortality, with decreased survival from 75% and 62.5% to 50%, respectively. Results obtained from serial liver scintigraphy with 99mTc-diisopropyl iminodiacetic acid (DISIDA) on single-photon emission computed tomography analysis showed that both liver uptake and excretion times of DISIDA were significantly delayed in LPS/D-GalN-treated animals and were effectively recovered by DET and silymarin treatment. This report demonstrates that DET functions in the modulating multiple molecular targets or signaling pathways that counteract inflammation during the progression of fulminant hepatitis and may serve as a novel lead compound for future development of anti-inflammatory or hepatoprotective agents.

Using microdialysis to analyse the passage of monovalent nanobodies through the blood-brain barrier.

Nanobodies are promising antigen-binding moieties for molecular imaging and therapeutic purposes because of their favourable pharmacological and pharmacokinetic properties. However, the capability of monovalent nanobodies to reach targets in the CNS remains to be demonstrated. We have assessed the blood-brain barrier permeability of Nb_An33, a nanobody against the Trypanosoma brucei brucei variant-specific surface glycoprotein (VSG). This analysis was performed in healthy rats and in rats that were in the encephalitic stage of African trypanosomiasis using intracerebral microdialysis, single photon emission computed tomography (SPECT) or a combination of both methodologies. This enabled the quantification of unlabelled and (99m) Tc-labelled nanobodies using, respectively, a sensitive VSG-based nanobody-detection elisa, radioactivity measurement in collected microdialysates and SPECT image analysis. The combined read-out methodologies showed that Nb_An33 was detected in the brain of healthy rats following i.v. injection, inflammation-induced damage to the blood-brain barrier, as in the late encephalitic stage of trypanosomiasis, significantly increased the efficiency of passage of the nanobody through this barrier. Complementing SPECT analyses with intracerebral microdialysis improved analysis of brain disposition. There is clear value in assessing penetration of the blood-brain barrier by monovalent nanobodies in models of CNS inflammation. Our data also suggest that rapid clearance from blood might hamper efficient targeting of specific nanobodies to the CNS. Nanobodies can enter the brain parenchyma from the systemic circulation, especially in pathological conditions where the blood-brain barrier integrity is compromised.