Abstract: The field of nuclear cardiology is witnessing growing interest in the use of cardiac PET for the evaluation of patients with coronary artery disease (CAD). The available evidence suggests that myocardial perfusion PET provides an accurate means for diagnosing obstructive CAD, which appears superior to SPECT especially in the obese and in those undergoing pharmacologic stress. The ability to record changes in left ventricular function from rest to peak stress and to quantify myocardial perfusion (in mL/min/g of tissue) provides an added advantage over SPECT for evaluating multivessel CAD. There is growing and consistent evidence that gated myocardial perfusion PET also provides clinically useful risk stratification. Although the introduction of hybrid PET/CT technology offers the exciting possibility of assessing the extent of anatomic CAD (CT coronary angiography) and its functional consequences (ischemic burden) in the same setting, there are technical challenges in the implementation of CT-based transmission imaging for attenuation correction. Nonetheless, this integrated platform for assessing anatomy and biology offers a great potential for translating advances in molecularly targeted imaging into humans.

Abstract: BACKGROUND AND PURPOSE: Glioblastoma multiforme (GBM) and single brain metastasis (MET) are the 2 most common malignant brain tumors that can appear similar on anatomic imaging but require vastly different treatment strategy. The purpose of our study was to determine whether the peak height and the percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MR imaging could differentiate GBM and MET. MATERIALS AND METHODS: Forty-three patients with histopathologic diagnosis of GBM ( n = 27) or MET ( n = 16) underwent DSC perfusion MR imaging in addition to anatomic MR imaging before surgery. Regions of interest were drawn around the nonenhancing peritumoral T2 lesion (PTL) and the contrast-enhancing lesion (CEL). T2* signal intensity-time curves acquired during the first pass of gadolinium contrast material were converted to the changes in relaxation rate to yield T2* relaxivity (ΔR2*) curve. The peak height of maximal signal intensity drop and the percentage of signal intensity recovery at the end of first pass were measured for each voxel in the PTL and CEL regions of the tumor. RESULTS: The average peak height for the PTL was significantly higher ( P = .04) in GBM than in MET. The average percentage of signal intensity recovery was significantly reduced in PTL (78.4% versus 82.8%; P = .02) and in CEL (62.5% versus 80.9%, P < .01) regions of MET compared with those regions in the GBM group. CONCLUSIONS: The findings of our study show that the peak height and the percentage of signal intensity recovery derived from the ΔR2* curve of DSC perfusion MR imaging can differentiate GBM and MET.

Abstract: Structural MRI and functional imaging by SPECT as well as 18F-FDG PET are widely used in the diagnosis of Alzheimer9s disease (AD). Metabolic and perfusion reductions in the parietotemporal association cortex are recognized as a diagnostic pattern for AD. Outstanding progress in the diagnostic accuracy of these modalities has been achieved with statistical analysis on a voxel-by-voxel basis after anatomic standardization of individual scans to a standardized brain volume template instead of visual inspection or a volume-of-interest technique. In a very early stage of AD, this statistical approach revealed losses of gray matter in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex and precuneus. This statistical approach also offers a prediction of the conversion from mild cognitive impairment (MCI) to AD. The presence of hypometabolism or hypoperfusion in parietal association areas and entorhinal atrophy at the MCI stage have been reported to predict a rapid conversion to AD. A recent advance in voxel-based statistical analysis has markedly enhanced the value of brain perfusion SPECT in diagnosing early AD at the stage of MCI.

Abstract: Forty-two stroke patients successively underwent perfusion CT (PCT)/CT angiography (CTA) and MRI examinations within 3 to 9 hours following symptom onset; 14 would have been suitable candidates for reperfusion treatment based on MRI findings. Correlation between PCT/CTA and MRI was excellent for infarct size, cortical involvement, and internal cerebral artery occlusion and substantial for penumbra/infarct ratio. Relying on MRI or PCT/CTA would have led to the same treatment decisions in all cases but one.

Abstract: Diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) provide useful data for tumor evaluation To assess the contribution of these multimodal techniques in grading glial neoplasms, we compared the value of DWI, PWI and MRS in the evaluation of histologically proven high- and low-grade gliomas in a population of 105 patients Independently for each modality, the following variables were used to compare the tumors: minimum apparent diffusion coefficient (ADC) and maximum relative cerebral blood volume (rCBV) normalized values between tumor and healthy tissue, maximum Cho/Cr ratio and minimum NAA/Cr ratio in tumor, and scored lactate and lipid values in tumor The Mann-Whitney and Wilcoxon tests were employed to compare DWI, PWI and MRS between tumor types Logistic regression analysis was used to determine which parameters best increased the diagnostic accuracy in terms of sensitivity, specificity, and positive and negative predictive values ROC curves were determined for parameters with high sensitivity and specificity to identify threshold values to separate high- from low-grade lesions Statistically significant differences were found for rCBV tumor/normal tissue ratio, and NAA/Cr ratio in tumor and Cho/Cr ratio in tumor between low- and high-grade tumors The best performing single parameter for group classification was the normalized rCBV value; including all parameters, statistical significance was reached by rCBV tumor/normal tissue ratio, NAA/Cr tumor ratio and lactate From the ROC curves, a high probability for a neoplasm to be a high-grade lesion was associated with a rCBV tumor/normal tissue ratio of >116 and NAA/Cr tumor ratio of <044 Combining PWI and MRS with conventional MR imaging increases the accuracy of the attribution of malignancy to glial neoplasms The best performing parameter was found to be the perfusion level

Abstract: Purpose: To prospectively monitor changes in rectal cancer perfusion after combined neoadjuvant chemotherapy and radiation therapy with perfusion computed tomography (CT) and to evaluate whether perfusion CT findings correlate with response to therapy. Materials and Methods: The study was approved by the institutional ethics committee of the European Institute of Oncology; written informed consent was obtained from all participants before the study. Twenty-five patients with rectal adenocarcinoma (18 men, seven women; age range, 42–72 years; mean age, 61.3 years) underwent perfusion CT; all of them underwent neoadjuvant chemotherapy and radiation therapy, followed by surgery. In 19 patients, perfusion CT was repeated after chemotherapy and radiation therapy. Dynamic perfusion CT was performed for 50 seconds after intravenous injection of contrast medium (40 mL, 370 mg iodine per milliliter, 4 mL/sec). Blood flow (BF), blood volume (BV), mean transit time, and permeability–surface area product (PS) were co...

Abstract: 3-(6-Methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime (11C-ABP688), a noncompetitive and highly selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), was evaluated for its potential as a PET agent. Methods: Six healthy male volunteers (mean age, 25 y; range, 21–33 y) were studied. Brain perfusion (15O-H2O) was measured immediately before each 11C-ABP688 PET scan. For anatomic coregistration, T1-weighted MRI was performed on each subject. Arterial blood samples for the determination of the arterial input curve were obtained at predefined time points, and 11C-ABP688 uptake was assessed quantitatively using a 2-tissue-compartment model. Results: An initial rapid uptake of radioactivity followed by a gradual clearance from all examined brain regions was observed. Relatively high radioactivity concentrations were observed in mGluR5-rich brain regions such as the anterior cingulate, medial temporal lobe, amygdala, caudate, and putamen, whereas radioactivity uptake in the cerebellum and white matter, regions known to contain low densities of mGluR5, was low. Specific distribution volume as an outcome measure of mGluR5 density in the various brain regions ranged from 5.45 ± 1.47 (anterior cingulate) to 1.91 ± 0.32 (cerebellum), and the rank order of the corresponding specific distribution volumes of 11C-ABP688 in cortical regions was temporal > frontal > occipital > parietal. The metabolism of 11C-ABP688 in plasma was rapid; at 60 min after injection, 25% ± 0.03% of radioactivity measured in the plasma of healthy volunteers was intact parent compound. Conclusion: The results of these studies indicate that 11C-ABP688 has suitable characteristics and is a promising PET ligand for imaging mGluR5 distribution in humans. Furthermore, it could be of great value for the selection of appropriate doses of clinically relevant candidate drugs that bind to mGluR5 and for PET studies of patients with psychiatric and neurologic disorders.

Abstract: Combining the functional information of SPECT myocardial perfusion imaging (SPECT-MPI) and the morphological information of coronary CT angiography (CTA) may allow easier evaluation of the spatial relationship between coronary stenoses and perfusion defects. The aim of the present study was the validation of a novel software solution for three-dimensional (3D) image fusion of SPECT-MPI and CTA. SPECT-MPI with adenosine stress/rest 99mTc-tetrofosmin was fused with 64-slice CTA in 15 consecutive patients with a single perfusion defect and a single significant coronary artery stenosis (≥50% diameter stenosis). 3D fused SPECT/CT images were analysed by two independent observers with regard to superposition of the stenosed vessel onto the myocardial perfusion defect. Interobserver variability was assessed by recording the X, Y, Z coordinates for the origin of the stenosed coronary artery and the centre of the perfusion defect and measuring the distance between the two landmarks. SPECT-MPI revealed a fixed defect in seven patients, a reversible defect in five patients and a mixed defect in three patients and CTA documented a significant stenosis in the respective subtending coronary artery. 3D fused SPECT/CT images showed a match of coronary lesion and perfusion defect in each patient and the fusion process took less than 15 min. Interobserver variability was excellent for landmark detection (r = 1.00 and r = 0.99, p < 0.0001) and very good for the 3D distance between the two landmarks (r = 0.94, p < 0.001). 3D SPECT/CT image fusion is feasible, reproducible and allows correct superposition of SPECT segments onto cardiac CT anatomy.

Abstract: BACKGROUND AND PURPOSE: Perfusion imaging using CT can provide additional information about tumor vascularity and angiogenesis for characterizing gliomas. The purpose of our study was to demonstrate the usefulness of various perfusion CT (PCT) parameters in assessing the grade of treatment-naive gliomas and also to compare it with conventional MR imaging features. MATERIALS AND METHODS: PCT was performed in 19 patients with glioma (14 high-grade gliomas and 5 low-grade gliomas). Normalized ratios of the PCT parameters (normalized cerebral blood volume [nCBV], normalized cerebral blood flow [nCBF], normalized mean transit time [nMTT]) were used for final analysis. Conventional MR imaging features of these tumors were assessed separately and compared with PCT parameters. Low- and high-grade gliomas were compared by using the nonparametric Wilcoxon 2-sample tests. RESULTS: Mean nCBV in the high- and low-grade gliomas was 3.06 ± 1.35 and 1.44 ± 0.42, respectively, with a statistically significant difference between the 2 groups (P = .005). Mean nCBF for the high- and low-grade gliomas was 3.03 ± 2.16 and 1.16 ± 0.36, respectively, with a statistically significant difference between the 2 groups (P = .045). Cut points of >1.92 for nCBV (85.7% sensitivity and 100% specificity), >1.48 for nCBF (71.4% sensitivity and 100% specificity), and 1.92 or nCBF of >1.48 improved the sensitivity and specificity to 92.9% and 100%, respectively. The sensitivity and specificity for diagnosing a high-grade glioma with conventional MR imaging were 85.7% and 60%, respectively. CONCLUSIONS: PCT can be used for preoperative grading of gliomas and can provide valuable complementary information about tumor hemodynamics, not available with conventional imaging techniques. nCBV was the single best parameter correlating with glioma grades, though using nCBF when nCBV was 1.92 was found to identify the high-grade gliomas.

Abstract: BACKGROUND AND PURPOSE: Treatment of advanced stage squamous cell carcinoma of the upper aerodigestive tract with nonsurgical organ preservation protocols demonstrates improved cure rates with fewer comorbidities compared with surgery and radiation. The purpose of this study was to prospectively assess whether pretreatment evaluation of the primary site with quantitative CT perfusion measurements predicted response to induction chemotherapy and to create a prediction model to predict the response to induction chemotherapy in future patients. METHODS: Seventeen patients who were enrolled in a prospective trial assessing surgical intervention versus a nonsurgical protocol underwent a pretreatment CT perfusion followed by direct laryngoscopy. After induction chemotherapy, tumor response was determined by the surgeon’s estimate of tumor volume. The CT perfusion parameters were correlated with the clinical response using a Wilcoxon rank-sum analysis. A logistic regression model was used to create a prediction based on the most significant CT perfusion parameter. RESULTS: Elevated values of blood volume (P = .004) and blood flow (P = .03) were significantly correlated with >50% reduction in tumor volume after chemotherapy. A prediction model based on tumor blood volume demonstrated 91.7% sensitivity and 80.0% specificity, with an area under the receiver operating characteristic curve of 0.95. CONCLUSION: Our preliminary data imply that tumors with elevated blood volume and blood flow were statistically associated with response to induction chemotherapy. These results suggest that pretreatment CT perfusion may be able to identify patients who will successfully respond to induction chemotherapy, which could potentially eliminate this step for subsequent patients when deciding on the appropriate treatment regimen.

Abstract: We hypothesized that myocardial perfusion imaging (MPI) would fail to identify all vascular zones with the potential for myocardial ischemia in patients with multivessel coronary disease (MVD). MPI is based on the concept of relative flow reserve. The ability of these techniques to determine the significance of a particular stenosis in the setting of MVD is questionable. Fractional flow reserve (FFR) can determine the significance of individual stenoses. Thirty-six patients with disease involving 88 arteries underwent angiography, FFR, and MPI. FFR was performed using a pressure wire with hyperemia from intracoronary adenosine. Myocardial perfusion images were analyzed quantitatively and segments assigned to a specific coronary artery. The relation between FFR and perfusion was determined for each vascular zone. Of the 88 vessels, the artery was occluded (n = 20) or had an abnormal FFR ≤0.75 (n = 34) in 54 of 88 (61%). MPI showed no defect in 51 zones (58%). Concordance between angiography, FFR, and MPI was seen in 61 of 88 zones (69%). Discordance was seen in the remaining 27 zones (31%) and was predominantly from the finding of a FFR

Abstract: Head injury remains an important cause of death and disability in young adults. This review will discuss the role of structural imaging using computed tomography (CT) and magnetic resonance imaging (MRI) and physiological imaging using CT perfusion, 131 Xe CT, MRI and spectroscopy (MRS), single photon emission computed tomography, and positron emission tomography (PET) in the assessment, management, and prediction of outcome after head injury. CT allows rapid assessment of brain pathology which ensures patients who require urgent surgical intervention receive appropriate care. Although MRI provides greater spatial resolution, particularly within the posterior fossa and deep white matter, a complete assessment of the burden of injury requires imaging of cerebral physiology. Physiological imaging techniques can only provide ‘snap shots’ of physiology within the injured brain, but they can be repeated, and such data can be used to assess the impact of therapeutic interventions. Perfusion imaging based on CT techniques (xenon CT and CT perfusion) can be implemented easily in most hospital centres, and provide quantitative perfusion data in addition to structural images. PET imaging provides unparalleled insights into cerebral physiology and pathophysiology, but is not widely available and is primarily a research tool. MR technology continues to develop and is becoming generally available. Using a complex variety of sequences, MR can provide data concerning both structural and physiological derangements. Future developments with such imaging techniques should improve understanding of the pathophysiology of brain injury and provide data that should improve management and prediction of functional outcome.

Abstract: Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC) Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT) The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung) Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 22 and 42 Gy, respectively, compared with those in the anatomic plans The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 71%, 60%, and 51%, respectively, for F50 lung, and 117%, 120%,more » and 68%, respectively, for F90 lung A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients« less

Abstract: Peripheral arterial disease (PAD) is a condition characterized by flow-limiting atherosclerosis in the vessels supplying the lower limbs. Currently, between eight and 12 million Americans are affected by PAD and the incidence is expected to rise as the population ages (1). As a consequence of impaired tissue perfusion, PAD patients can experience pain, diminished exercise capacity, and tissue loss, with some ultimately requiring amputation (2). Improving blood flow is a major therapeutic goal in patients with PAD and a number of innovative approaches beyond revascularization have been investigated, although effective pharmacologic therapies that increase tissue perfusion are still lacking (3–5). A noninvasive technique capable of measuring tissue perfusion would be of great clinical value for assessing the severity of PAD and monitoring response to novel therapeutic interventions designed to enhance skeletal muscle perfusion. First-pass gadolinium-enhanced MRI is a robust technique well validated for evaluating myocardial perfusion (6–9). First-pass gadolinium-enhanced MRI is performed using a T1-weighted sequence to visualize a gadolinium-based contrast agent in transit through tissue. Signal intensity changes in the muscle parallel contrast concentration, and time-intensity curves (TIC) can be generated in regions of interest. In myocardium, the TIC upslope correlates well with measures of micro-sphere blood flow (10–12). While first-pass gadolinium-enhanced MRI has been used to evaluate blood flow in skeletal muscle among healthy individuals under predominantly nonphysiologic stress (13,14), its utility in identifying and characterizing perfusion in patients with PAD has not been extensively explored. The purpose of this study was to develop and evaluate a novel MR approach for measuring skeletal muscle perfusion semiquantitatively during exercise-induced ischemia in both mild to moderate PAD patients and normal subjects following isometric exercise within the MR environment.

Abstract: I read with interest the recent article by Vermeltfoort et al , 1 on the use of dynamic contrast enhancement in MRI to evaluate the possible presence of subendocardial ischaemia in patients with chest pain and normal coronary arteries (‘syndrome X’) Their conclusion, that they found no evidence of subendocardial hypoperfusion with adenosine stress in these patients, is in striking contrast to a previous report by Panting et al , 2 who found evidence of a failure of the perfusion of the …

Abstract: BACKGROUND AND PURPOSE: Hypoperfusion of the normal-appearing white matter in multiple sclerosis (MS) may be related to ischemia or secondary to hypometabolism from wallerian degeneration (WD). This study evaluated whether correlating perfusion and diffusion tensor imaging (DTI) metrics in normal-appearing corpus callosum could provide support for an ischemic mechanism for hypoperfusion. MATERIALS AND METHODS: Fourteen patients with relapsing-remitting MS (RRMS) and 17 control subjects underwent perfusion MR imaging and DTI. Absolute measures of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated. Mean diffusivity (MD) and fractional anisotropy (FA) maps were computed from DTI data. After visual coregistration of perfusion and DTI images, regions of interest were placed in the genu, central body, and splenium of normal-appearing corpus callosum. Pearson product-moment correlation coefficients were calculated using mean DTI and perfusion measures in each region. RESULTS: In the RRMS group, CBF and CBV were significantly correlated with MD in the splenium ( r = 0.83 and r = 0.63, respectively; both P r = 0.86 and r = 0.65, respectively; both P r = 0.23 and 0.25, respectively; both P is nonsignificant). No significant correlations were found between MTT and DTI measures or between FA and any perfusion measure in the RRMS group. No significant correlations between diffusion and perfusion metrics were found in control subjects. CONCLUSION: In the normal-appearing corpus callosum of patients with RRMS, decreasing perfusion is correlated with decreasing MD. These findings are more consistent with what would be expected in primary ischemia than in secondary hypoperfusion from WD.

Abstract: Objective: To prospectively assess the diagnostic accuracy of CT perfusion (CTP) and transcranial Doppler sonography (TCD) for the prediction of secondary cerebral infarction (SCI) after aneurysmal subarachnoid hemorrhage (SAH). Methods: During 2 weeks after SAH, 38 consecutive patients completed an average of 3.5 CT/CTP and 10.7 TCD examinations at regular intervals as required by the study protocol. SCI was defined as delayed infarction on native CT between 3 and 14 days after SAH and developed in n = 14 patients (n = 24 without SCI). Analysis was based on examination dates before SCI. Common measures of diagnostic accuracy were calculated for qualitative CTP (visual color-map ratings from two blinded observers) and TCD assessments (mean flow velocity >120 cm/s in anterior, middle, and posterior cerebral artery territories). Quantitative measures, which for CTP were obtained from cortical a priori regions of interest corresponding to the vascular territories, were analyzed by binary logistic regression. Results: Time of prediction for SCI by CTP was at a median of 3 days (range 2 to 5 days) before manifestation of complete infarction on native CT. Visual assessment of time-to-peak (TTP) color maps performed best for the prediction of SCI with 0.93 sensitivity (95% CI: 0.7 to 1.0) and 0.67 specificity (95% CI: 0.53 to 0.7). On quantitative analysis, the odds ratio (OR) for 1 second of side-to-side delay in TTP was 1.4 ( p = 0.01, Wald χ 2 = 8.57, CI: 1.07 to 1.82). Daily TCD measures were not significantly related to SCI at any time before complete infarction on native CT. Conclusions: Time to peak as indicated by CT perfusion is a sensitive and early predictor of secondary cerebral infarction.

Abstract: Background The aim of the study was to assess (i) the rate of contrast-induced nephropathy (CIN), (ii) the amount and time course of renal dysfunction, (iii) the identification of risk factors and calculation of a risk score for CIN in acute stroke patients after CT perfusion (CTP) and CT angiography (CTA).

Abstract: Objective: To evaluate the feasibility of monitoring the autologous mononuclear bone marrow (ABMMN) cells implanted into the brain after acute ischemic stroke by the technique of labeling with Tc-99m-HMPAO. Case Report: A 37-year-old man presented with aphasia, right-side hypoesthesia, and right homonymous hemianopsia after an acute ischemic stroke of the left middle cerebral artery. He was included in an autologous bone marrow mononuclear cell-based therapy research protocol about the safety of intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke. Nine days after the stroke he received 3.0 × 107 ABMMN cells delivered into the left cerebral middle artery via a balloon catheter. Approximately 1% of these cells were labeled with 150 MBq (4 mCi) Tc-99m by incubation with hexamethylpropylene amine oxime (HMPAO). Results: Brain perfusion images with Tc-99m ECD demonstrated hypoperfusion in the left temporal and parietal regions. The perfusion brain images were compared with tomographic views of the brain obtained 8 hours after ABMMN-labeled cell delivery, revealing intense accumulation of the ABMMN-labeled cells in the ipsilateral hemisphere. A whole-body scan was done and showed left brain, liver, and spleen uptake. Conclusions: Our results showed that Tc-99m HMPAO can be used to label ABMMN cells for in vivo cell visualization, and that brain SPECT imaging with labeled ABMMN cells is a feasible noninvasive method for studying the fate of transplanted cells in vivo. Additionally, our findings demonstrate the localization of these intra-arterially injected cells.