Abstract: Current noninvasive tests for coronary artery disease detect atherosclerosis or regional ischemia Global myocardial flow reserve is not routinely identified, although it may be an additional marker of disease development and progression Methods: For the clinical work-up of suspected or known stable coronary artery disease, 275 individuals had undergone rest–dipyridamole 82Rb myocardial perfusion imaging using PET In addition to clinical measures of regional perfusion and function, an experimentally validated approach to quantify global myocardial flow reserve was used Follow-up was obtained for 362 ± 277 d Results: Myocardial blood flow and flow reserve showed significant correlation to systemic and cardiac hemodynamics and a weak association with risk factors such as age and history of hyperlipidemia Flow reserve was expectedly lower in subjects with regional ischemia (170 ± 065 vs 231 ± 097 in those without; P

Abstract: Objective: Cerebral perfusion imaging with computed tomography (CT) or magnetic resonance (MR) is widely available. The optimum perfusion values to identify tissue at risk of infarction in acute stroke are unclear. We systematically reviewed CT and MR perfusion imaging in acute ischemic stroke. Methods: We searched for papers on MR or CT perfusion performed <24 hours after stroke that assessed perfusion thresholds, mean perfusion lesion values, or lesion volumes. We extracted definitions and perfusion values. We compared definitions and evaluated perfusion thresholds for ‘‘nonviable’’/’’at risk’’ and ‘‘at risk’’/’’not at risk tissue’’ thresholds. Results: Among 7,152 papers, 69 met inclusion criteria for analysis of definitions (49 MR and 20 CT), 21 MR (n ¼ 551), and 10 CT (n ¼ 266) papers, median sample size 22, provided thresholds. We found multiple definitions for tissue states, eg, tissue at risk, 18; nonviable tissue, 12; 16, no definition. Perfusion parameters varied widely; eg, 9 different MR, 6 different CT parameters for the ‘‘at risk’’/’’not at risk threshold.’’ Median threshold values varied up to 4-fold, eg, for the ‘‘at risk’’/’’not at risk threshold,’’ median cerebral blood flow ranged from 18 to 37ml/100g/min; mean transit time from 1.8 to 8.3 seconds relative to the contralateral side. The influence of reperfusion and duration of ischemia could not be assessed. Interpretation: CT and MR perfusion imaging viability thresholds in stroke are derived from small numbers of patients, variable perfusion analysis methods and definitions of tissue states. Greater consistency of methods would help determine reliable perfusion viability values for wider clinical use of perfusion imaging. ANN NEUROL 2011;70:384–401

Abstract: Background— The standard interpretation of perfusion imaging is based on the assessment of relative perfusion distribution. The limitations of that approach have been recognized in patients with multivessel disease and endothelial dysfunction. To date, however, no large clinical studies have investigated the value of measuring quantitative blood flow and compared that with relative uptake. Methods and Results— One hundred four patients with moderate (30%–70%) pretest likelihood of coronary artery disease (CAD) underwent PET imaging during adenosine stress using 15O-water and dynamic imaging. Absolute myocardial blood flow was calculated from which both standard relative myocardial perfusion images and images scaled to a known absolute scale were produced. The patients and the regions then were classified as normal or abnormal and compared against the reference of conventional angiography with fractional flow reserve. In patient-based analysis, the positive predictive value, negative predictive value, and accuracy of absolute perfusion in the detection of any obstructive CAD were 86%, 97%, and 92%, respectively, with absolute quantification. The corresponding values with relative analysis were 61%, 83%, and 73%, respectively. In region-based analysis, the receiver operating characteristic curves confirmed that the absolute quantification was superior to relative assessment. In particular, the specificity and positive predictive value were low using just relative differences in flow. Only 9 of 24 patients with 3-vessel disease were correctly assessed using relative analysis. Conclusions— The measurement of myocardial blood flow in absolute terms has a significant impact on the interpretation of myocardial perfusion. As expected, multivessel disease is more accurately detected. Clinical Trial Registration— URL: . Unique identifier: [NCT00627172][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00627172&atom=%2Fcirccvim%2F4%2F6%2F678.atom

Abstract: Background and Purpose—Admission infarct core lesion size is an important determinant of management and outcome in acute (<9 hours) stroke. Our purposes were to: (1) determine the optimal CT perfus...

Abstract: Background— Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR). Methods and Results— Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64±10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate 63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv. Conclusions— Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.

Abstract: Background and Purpose—Current selection criteria for intra-arterial therapies in the anterior circulation use time windows of 8 hours. Modern neuroimaging techniques have identified individuals with salvageable penumbra who present beyond this timeframe. We sought to assess safety, procedural, and clinical outcomes of MRI or CT perfusion imaging-based endovascular therapy in patients with anterior circulation stroke treated beyond 8 hours from time last seen well. Methods—We conducted a multicenter retrospective review of consecutive patients meeting the following criteria: (1) acute proximal intracranial anterior circulation occlusion; (2) endovascular treatment initiated >8 hours from time last seen well; and (3) treatment selection based on MRI or CT perfusion imaging. Results—Two hundred thirty-seven patients were identified (mean age, 63.8±16 years; mean baseline National Institutes of Health Stroke Scale, 15±5.5; mean time last seen well to treatment, 15±11.2 hours; male gender, 46%). Successful re...

Abstract: Background Multiple lines of evidence suggest that cardiovascular co-morbidities hasten the onset of Alzheimer’s disease (AD) or accelerate its course. Methods To evaluate the utility of cerebral vascular physical function and/or condition parameters as potential systemic indicators of AD, transcranial Doppler (TCD) ultrasound was used to assess cerebral blood flow and vascular resistance of the 16 arterial segments comprising the circle of Willis and its major tributaries. Results Our study showed that decreased arterial mean flow velocity and increased pulsatility index are associated with a clinical diagnosis of presumptive AD. Cerebral blood flow impairment shown by these parameters reflects the global hemodynamic and structural consequences of a multifaceted disease process yielding diffuse congestive microvascular pathology, increased arterial rigidity, and decreased arterial compliance, combined with putative age-associated cardiovascular output declines. Conclusions TCD evaluation offers direct physical confirmation of brain perfusion impairment and might ultimately provide a convenient and a noninvasive means to assess the efficacy of medical interventions on cerebral blood flow or reveal incipient AD. In the near term, TCD-based direct assessments of brain perfusion might offer the prospect of preventing or mitigating AD simply by revealing patients who would benefit from interventions to improve circulatory system function.

Abstract: Perfusion imaging of brain tumors has been performed by using various tracer and nontracer modalities and can provide additional physiologic and hemodynamic information, which is not available with routine morphologic imaging. Tumor vascular perfusion parameters obtained by using CT or MR perfusion have been used for tumor grading, prognosis, and treatment response in addition to differentiating treatment/radiation effects and non-neoplastic lesions from neoplasms. This article is an overview of the utility of PCT for assessment of brain tumors and describes the technique, its advantages, and limitations.

Abstract: Background— The clinical course in pulmonary arterial hypertension (PAH) is variable, and there is limited information on the determinants and progression of right ventricular (RV) dysfunction. The objective is to develop PET metabolic imaging of the RV as a noninvasive tool in patients with PAH. Methods and Results— We performed PET scanning in 16 patients with idiopathic PAH (age, 41±14 years, 82% women) using 13N-NH3 for perfusion imaging and 18F-fluorodeoxyglucose for metabolic imaging. The myocardium was divided into 6 regions of interest (3 left ventricular [LV], 3 RV), and time-activity curves were generated. A 2- compartment model was used to calculate myocardial blood flow (MBF), and Patlak analysis was used to calculate the rate of myocardial glucose uptake (MGU). All patients underwent cardiac catheterization, cardiac MRI, and cardiopulmonary exercise testing with gas exchange. MBF, MGU, and the ratio of RV/LV MGU were correlated to clinical parameters. Pulmonary artery (PA) pressure was 79±19/30±8 mm Hg (mean, 48±10 mm Hg). MBF was 0.84±0.33 mL/g per minute for the LV and 0.45±0.14 mL/g per minute for the RV. Mean MGU was 136±72 nmol/g per minute for the LV and 96±69 nmol/g per minute for the RV. The ratio of RV/LV MGU correlated significantly with PA systolic ( r =0.75, P =0.0085) and mean ( r =0.87, P =0.001) pressure and marginally with maximum oxygen consumption ( r =−0.59, P =0.05). RV free wall MGU also correlated well with mean PA pressure ( r =0.66, P =0.03). Conclusions— PET scanning with 13N-NH3 and 18F-fluorodeoxyglucose is a feasible modality for quantifying RV blood flow and metabolism in patients with idiopathic PAH.

Abstract: Objective:The goal of this research project was to develop a volumetric strategy for real-time monitoring and characterization of tumor blood flow using microbubble contrast agents and ultrasound (US) imaging.Materials and Methods:Volumetric contrast-enhanced US (VCEUS) imaging was implemented on a

Abstract: Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region.

Abstract: OBJECTIVE: We analyzed the diffusion and perfusion characteristics of acute MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) lesions in a large series to investigate the controversial changes of the apparent diffusion coefficient (ADC) that were reported in prior studies. MATERIALS AND METHODS: We analyzed 44 newly appearing lesions during 28 stroke-like episodes in 13 patients with MELAS. We performed a visual assessment of the MR images including the ADC and perfusion maps, comparison of the ADC between the normal and abnormal areas, comparison of % ADC between the 44 MELAS lesions and the 30 acute ischemic infarcts. In addition, the patterns of evolution on follow-up MR images were analyzed. RESULTS: Decreased, increased, and normal ADCs were noted in 16 (36%), 16 (36%), and 12 (27%) lesions, respectively. The mean % ADC was 102 ± 40.9% in the MELAS and 64 ± 17.8% in the acute vascular infarcts (p < 0.001), while perfusion imaging demonstrated hyper-perfusion in six acute MELAS lesions. On follow-up images, resolution, progression, and tissue loss were noted in 10, 4, and 17 lesions, respectively. CONCLUSION: The cytotoxic edema gradually evolves following an acute stroke-like episode in patients with MELAS, and this may overlap with hyper-perfusion and vasogenic edema. The edematous swelling may be reversible or it may evolve to encephalomalacia, suggesting irreversible damage.

Abstract: Background and Purpose—The value of multimodal CT to assist thrombolysis has received little attention in stroke. Methods—We assessed prospectively the impact derived from the routine application of CT perfusion and CTA in patients with acute stroke treated consecutively with alteplase. The safety and efficacy of thrombolytic therapy were compared in 106 patients assisted with CT/CTA/CT perfusion (multimodal CT group) and 262 patients assisted without full multimodal brain imaging (control group) during a 5-year period (2005–2009). Results—Good outcome (modified Rankin scale score ≤2) at 3 months was increased in the multimodal group compared with controls (adjusted OR, 2.88; 95% CI, 1.50–5.52). Multimodal-assisted thrombolysis yielded superior benefits in patients treated beyond 3 hours (adjusted OR, 4.48; 95% CI, 1.68–11.98) than treated within 3 hours (adjusted OR, 1.31; 95% CI, 0.80–2.16; interaction test P=0.043). Mortality (14% and 15%) and symptomatic hemorrhage (5% and 7%) were similar in both gro...

Abstract: Three-dimensional myocardial perfusion imaging requires significant acceleration of data acquisition to achieve wholeheart coverage with adequate spatial and temporal resolution. The present article introduces a compartment-based k-t principal component analysis reconstruction approach, which permits three-dimensional perfusion imaging at 10-fold nominal acceleration. Using numerical simulations, it is shown that the compartment-based method results in accurate representations of dynamic signal intensity changes with significant improvements of temporal fidelity in comparison to conventional k-t principal component analysis reconstructions. Comparison of the two methods based on rest and stress threedimensional perfusion data acquired with 2.3 3 2.3 3 10 mm 3 during a 225 msec acquisition window in patients confirms the findings and demonstrates the potential of compartmentbased k-t principal component analysis for highly accelerated three-dimensional perfusion imaging. Magn Reson Med 65:575–587, 2011. V C 2010 Wiley-Liss, Inc.

Abstract: Objective To assess the value of left ventricular (LV) dyssynchrony, using phase analysis of nuclear single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) as independent predictor of cardiac events. Methods Phase analysis using Emory Cardiac Toolbox was applied on gated rest MPI scans to assess LV dyssynchrony in a total of 202 patients. Follow-up was obtained in 197 patients (97.5%). Major adverse cardiac events (MACE) (cardiac death and hospitalisation for any cardiac reasons, including worsening of heart failure, non-fatal myocardial infarction, unstable angina and coronary revascularisation) were determined using the Kaplan–Meier method. Cox proportional hazard regression was used to identify independent predictors of cardiac events. Results At a median follow-up of 3.2±1.2 years, 41 patients had at least one event, including 5 cardiac deaths. LV dyssynchrony (n=35) was associated with a significantly higher incidence of MACE (p Conclusion LV dyssynchrony assessed by phase analysis of gated SPECT-MPI is a strong predictor of MACE independent of other known predictors such as perfusion defects or decreased LV ejection fraction.

Abstract: Background— A novel technology has been developed for ultrafast (UF) single-photon emission CT (SPECT) myocardial perfusion imaging by using a pinhole collimation design and multiple cadmium zinc telluride crystal arrays. The purpose of this study was to compare myocardial perfusion imaging obtained by UF-SPECT with standard (S) SPECT in patients with known or suspected coronary artery disease. Methods and Results— A total of 34 patients underwent single-day 99mTc-tetrofosmin stress/rest myocardial perfusion imaging. UF-SPECT was performed 10 minutes before S-SPECT. Images were qualitatively analyzed, and the summed stress score and summed rest score were calculated. The segmental tracer uptake value (percentage of maximum myocardial uptake) also was quantified for both UF- and S-SPECT. When only 29 of 34 patients with significant coronary lesions were analyzed, the summed stress score was 10.1±4.4 versus 6.4±2.9, respectively, for UF- and S-SPECT ( P =0.002). Qualitative and quantitative per-patient analysis showed similar results in detection of coronary artery disease for UF- and S-SPECT. In contrast, per-vessel analysis demonstrated higher regional sensitivity of UF- versus S-SPECT. UF-SPECT showed higher sensitivity in detecting multivessel disease ( P =0.003) versus S-SPECT. Conclusions— This pilot study confirms that UF-SPECT provides high-quality fast myocardial perfusion imaging and suggests that it may allow a more-accurate evaluation of both extent and severity of myocardial ischemia in patients with coronary artery disease.

Abstract: We present six cases of extra-axial lesions: three meningiomas [including one intraventricular and one cerebellopontine angle (CPA) meningioma], one dural metastasis, one CPA schwannoma and one choroid plexus papilloma which were chosen from a larger cohort of extra-axial tumors evaluated in our institution. Apart from conventional MR examinations, all the patients also underwent perfusion-weighted imaging (PWI) using dynamic susceptibility contrast method on a 1.5 T MR unit (contrast: 0.3 mmol/kg, rate 5 ml/s). Though the presented tumors showed very similar appearance on conventional MR images, they differed significantly in perfusion examinations. The article draws special attention to the usefulness of PWI in the differentiation of various extra-axial tumors and its contribution in reaching final correct diagnoses. Finding a dural lesion with low perfusion parameters strongly argues against the diagnosis of meningioma and should raise a suspicion of a dural metastasis. In cases of CPA tumors, a lesion with low relative cerebral blood volume values should be suspected to be schwannoma, allowing exclusion of meningioma to be made. In intraventricular tumors arising from choroid plexus, low perfusion parameters can exclude a diagnosis of meningioma. In our opinion, PWI as an easy and quick to perform functional technique should be incorporated into the MR protocol of all intracranial tumors including extra-axial neoplasms.

Abstract: The cytochrome P450 2D6 (CYP2D6) is a genetically polymorphic enzyme involved in the metabolism of several psychoactive drugs. Beside its expression in the liver, CYP2D6 is highly expressed in several regions of the brain, such as the hippocampus, thalamus, hypothalamus and the cortex, but its function in the brain is not well understood. The CYP2D6 enzyme may also have a physiological role due to its involvement in neurotransmitter biotransformation. In this study, CYP2D6 genotyping was performed in N=188 healthy individuals and compared with brain perfusion levels at rest, which may reflect an ongoing biological process regulating the reactivity of the individual to emotional stimuli and the detection of signals evoking fear. Relative to N=42 matched extensive metabolizers, N=14 poor metabolizers were associated with 15% higher perfusion levels in the thalamus (P=0.03 and 0.003). Effects were also present in the whole (N=188) sample divided into metabolizer groups, or finely graded into seven CYP2D6 activity levels. A weaker effect was observed in the right hippocampus (P=0.05). An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain.

Abstract: Basic knowledge of active and passive transport mechanisms for concentrating monovalent cations in myocardial cells led to the investigation of the application of radioisotopes of potassium, thallium, rubidium, and ammonia to the in vivo noninvasive assessment of regional myocardial perfusion and viability utilizing gamma camera or positron emission tomographic (PET) imaging technology. Subsequently, technetium-99m (Tc-99m)-labeled isonitriles (sestamibi and tetrofosmin), which bind to mitochondrial membranes, emerged as superior imaging agents with single photon emission tomography (SPECT) imaging. When any of these imaging agents are injected intravenously during either exercise or pharmacologic stress, myocardial defects in tracer uptake represent either abnormal regional flow reserve or myocardial scar reflecting of coronary artery disease (CAD). The major clinical indications for stress SPECT or PET myocardial perfusion imaging are for detection of CAD as the cause of chest pain and risk stratification for prognostication. Patients with normal stress myocardial perfusion scans have an excellent prognosis with 50% uptake compared to normal uptake have a better long-term outcome with revascularization than with medical therapy with enhanced left ventricular function and improved survival. Other applications of SPECT imaging include the evaluation of cardiac sympathetic function, assessment of myocardial metabolism in health and disease, and molecular imaging of coronary atherosclerosis and myocardial stem cell therapy.