This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia.This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent serial rest/adenosine stress Rubidium-82 MPI sessions. Mean bolus transit times (MBTT) were obtained by calculating the time delay from the Rubidium-82 bolus arrival in the pulmonary trunk to the arrival in the left myocardial atrium. Using the MBTT, in combination with stroke volume (SV) and heart rate (HR), we estimated pulmonary blood volume (PBV = (SV × HR) × MBTT). We report the empirically measured MBTT, HR, SV, and PBV, all stratified by sex [male (M) vs female (F)] as mean (SD). In addition, we report grouped repeatability measures using the within-subject repeatability coefficient.Mean bolus transit times was shortened during adenosine stressing with sex-specific differences [(seconds); Rest: Female (F) = 12.4 (1.5), Male (M) = 14.8 (2.8); stress: F = 8.8 (1.7), M = 11.2 (3.0), all P ≤ 0.01]. HR and SV increased during stress MPI, with a concomitant increase in the PBV [mL]; Rest: F = 544 (98), M = 926 (105); Stress: F = 914 (182), M = 1458 (338), all P < 0.001. The following test–retest repeatability measures were observed for MBTT (Rest = 17.2%, Stress = 17.9%), HR (Rest = 9.1%, Stress = 7.5%), SV (Rest = 8.9%, Stress = 5.6%), and for PBV measures (Rest = 20.7%, Stress = 19.5%)Pulmonary blood volume can be extracted by cardiac rubidium-82 MPI with excellent test–retest reliability, both at rest and during adenosine-induced hyperemia.

Cardiac arrest (CA) is a fatal disease with high rates of neurological impairment. At present, targeted temperature management (TTM) is the only strategy with firm clinical evidence to prove its effectiveness. However, there is still controversy on the implementation of TTM, particularly on its depth, with a lack of elucidated underlying therapeutic mechanisms. Six Wistar rats were subjected to 8 min asphyxia-CA and randomly divided into TTM at $33^{\mathrm{o}}\mathrm{C}(\mathrm{n}=3)$ or $35^\circ \mathrm{C}$ groups $(\mathrm{n}=3)$. The spatiotemporal characteristics of cerebral glucose metabolism after CA were investigated by 18F-FDG microPET/CT. Myelin Basic Protein (MBP) immunofluorescence staining was used to assess acute injury and recovery of oligodendrocytes. Functional recovery was evaluated using the neurological deficit score (NDS). There was a significant improvement in functional recovery by NDS (p < 0.05) in the $33^{\mathrm{o}}\mathrm{C}$ group compared with the $35^\circ \mathrm{C}$ group. Glucose metabolism of the $33^\circ \mathrm{C}$ group was higher than that of the $35^{\mathrm{o}}\mathrm{C}$ group early after resuscitation (within 10 minutes). Immunofluorescence analysis showed that positive MBP signals in the cortex and hippocampus in the $33^{\mathrm{o}}\mathrm{C}$ group were greater than in the $35^{\mathrm{o}}\mathrm{C}$ group. In conclusion, compared to $35^{\mathrm{o}}\mathrm{C}$ TTM, $33^\circ \mathrm{C}$ TTM changed the spatiotemporal characteristics of brain glucose metabolisms with improved neurological function, which may be through oligodendrocyte participation.

Purpose We sought to study the predictive value of the metabolic heterogeneous zone (HZ) as determined by (18)Fluorodeoxyglucose ((18)FDG) positron emission tomography (PET) viability studies in ventricular tachycardia (VT) patients. Methods PET studies utilizing (82)Rubidium (Rb-82) tracer for perfusion and (18)FDG tracer for viability were analyzed using PMOD (PMOD Technologies) and further analyzed using 684-segment plots. (18)FDG uptake was normalized to the area with maximal perfusion on the rest Rb-82 study. Metabolic scar, HZ, and healthy segments were defined with perfusion-normalized (18)FDG uptake between 0%-50%, 50%-70%, and >70%, respectively. Results Thirty-four VT patients (age, 63 +/- 12 years) were evaluated with (18)FDG-PET viability study. Most (n = 31) patients underwent VT ablation. Patients were categorized to HZ < median versus HZ >= median based on a median HZ area size of 21.0 cm(2). HZ size was significantly larger in the deceased group than the alive group (35.2 cm(2) vs. 18.1 cm(2), p = .01). Deaths were significantly higher in HZ >= 21 cm(2) group than HZ < 21 cm(2) group (58.8% vs. 11.8%, p = .005). Survival analysis showed significantly higher mortality in the HZ >= 21 cm(2) group than the HZ < 21 cm(2) group (HR = 4.1, 95% CI: 1.3-12.6, p = .016). In a multivariable analysis, HZ was found to be an independent predictor for all-cause mortality (HR = 1.07, 95% CI: 1.02-1.12, p = .01) Conclusions Increased HZ size of myocardium was associated with increased mortality. Metabolic HZ quantification may be of value in risk stratification and management of ischemic and nonischemic patients with VT.

The functional and molecular imaging characteristics of ischemic ventricular tachycardia (VT) substrate are incompletely understood. Our objective was to compare regional 18F-FDG PET tracer uptake with detailed electroanatomic maps (EAMs) in a more extensive series of postinfarction VT patients to define the metabolic properties of VT substrate and successful ablation sites. Methods: Three-dimensional (3D) metabolic left ventricular reconstructions were created from perfusion-normalized 18F-FDG PET images in consecutive patients undergoing VT ablation. PET defects were classified as severe (defined as <50% uptake) or moderate (defined as 50%-70% uptake), as referenced to the maximal 17-segment uptake. Color-coded PET scar reconstructions were coregistered with corresponding high-resolution 3D EAMs, which were classified as indicating dense scarring (defined as voltage < 0.5 mV), normal myocardium (defined as voltage > 1.5 mV), or border zones (defined as voltage of 0.5-1.5 mV). Results: All 56 patients had ischemic cardiomyopathy (ejection fraction, 29% ± 12%). Severe PET defects were larger than dense scarring, at 63.0 ± 48.4 cm2 versus 13.8 ± 33.1 cm2 (P < 0.001). Similarly, moderate/severe PET defects (≤70%) were larger than areas with abnormal voltage (≤1.5 mV) measuring 105.1 ± 67.2 cm2 versus 56.2 ± 62.6 cm2 (P < 0.001). Analysis of bipolar voltage (23,389 mapping points) showed decreased voltage among severe PET defects (n = 10,364; 0.5 ± 0.3 mV) and moderate PET defects (n = 5,243; 1.5 ± 0.9 mV, P < 0.01), with normal voltage among normal PET areas (>70% uptake) (n = 7,782, 3.2 ± 1.3 mV, P < 0.001). Eighty-eight percent of VT channel or exit sites (n = 44) were metabolically abnormal (severe PET defect, 78%; moderate PET defect, 10%), whereas 12% (n = 6) were in PET-normal areas. Metabolic channels (n = 26) existed in 45% (n = 25) of patients, with an average length and width of 17.6 ± 12.5 mm and 10.3 ± 4.2 mm, respectively. Metabolic channels were oriented predominantly in the apex or base (86%), harboring VT channel or exit sites in 31%. Metabolic rapid-transition areas (>50% change in 18F-FDG tracer uptake/15 mm) were detected in 59% of cases (n = 33), colocalizing to VT channels or exit sites (15%) or near these sites (85%, 12.8 ± 8.5 mm). Metabolism-voltage mismatches in which there was a severe PET defect but voltage indicating normal myocardium were seen in 21% of patients (n = 12), 41% of whom were harboring VT channel or exit sites. Conclusion: Abnormal 18F-FDG uptake categories could be detected using incremental 3D step-up reconstructions. They predicted decreasing bipolar voltages and VT channel or exit sites in about 90% of cases. Additionally, functional imaging allowed detection of novel molecular tissue characteristics within the ischemic VT substrate such as metabolic channels, rapid-transition areas, and metabolism-voltage mismatches demonstrating intrasubstrate heterogeneity and providing possible targets for imaging-guided ablation.

Background: Functional/molecular imaging characteristics of ischemic ventricular tachycardia (VT) substrate are incompletely understood. Objective: Compare regional 18F-FDG - PET tracer uptake with detailed electroanatomic maps (EAM) in a more extensive series of post-infarction VT patients to define metabolic properties of the VT substrate/successful ablation sites. \n\nMethods: 3D metabolic left ventricular (LV) reconstructions were created from perfusion-normalized 18F-FDG images in consecutive patients undergoing VT ablation. Metabolic defects were defined as severe (\u003c50% uptake) or moderate (50-70% uptake) referenced to the maximal 17-segmental uptake. Color-coded PET scars reconstructions were co-registered with corresponding high-resolution 3D EAM. \n\nResults: All 56 patients had ischemic cardiomyopathy (EF=29±12%). Severe PET defect ( 70% (n = 7,782, 3.2±1.3mV, p 70%). Metabolic channels (n = 26) existed in 45% (n = 25) of patients with average length/width of 17.6±12.5mm/10.3±4.2mm. Metabolic channels were oriented apex/base (86%) predominantly, harboring VT channel/exit sites in 31%. Metabolic Rapid Transition Areas (RTA: \u003e50% change of 18F-FDG tracer uptake/15mm) were detected in 59% (n = 33) co-localizing to VT channels/exit sites (15%) or its proximity (85%, 12.8±8.5mm). Metabolism-voltage mismatches (MVM) with PET 1.5mV) were seen in 21% (n = 12) harboring VT channel/exit sites in 41% of patients. \n\nConclusion: Abnormal 18F-FDG uptake categories can be detected using incremental 3D step-up reconstructions. They predicted decreasing bipolar voltages and VT channel/exit sites in ~90%. Additionally, functional imaging allowed detecting novel molecular tissue characteristics within the ischemic VT substrate such as metabolic channels, RTA, and MVM demonstrating intra-substrate heterogeneity and providing possible targets for imaging-guided ablation.

1University of Maryland School of Medicine, Baltimore, MD 2University of Maryland School of Medicine

Introduction: Early-stage liver fibrosis is potentially reversible, but difficult to diagnose. Clinical management would be enhanced by the development of a non-invasive imaging technique able to identify hepatic injury early, before end-stage fibrosis ensues. The analog of the amino acid proline, cis-4-[18F]fluoro-L-proline ([18F]fluoro-proline), which targets collagenogenesis in hepatic stellate cells (HSC), was used to detect fibrosis. Methods: Acute steatohepatitis was induced in experimental animals by liquid ethanol diet for 8 weeks, intra-gastric binge feedings every 10th day along with lipopolysaccharide (LPS) injection. The control animals received control diet for 8 weeks and an equivalent volume of saline on the same schedule as the acute steatohepatitis model. First, in vitro cellular experiments were carried out to assess [3H]proline uptake by HSC, hepatocytes and Kupffer cells derived from rats with acute steatohepatitis (n = 14) and controls (n = 14). Next, ex vivo liver experiments were done to investigate unlabeled proline-mediated collagen synthesis and its associated proline transporter expression in acute steatohepatitis (n = 5) and controls (n = 5). Last, in vivo dynamic and static [18F]fluoro-proline micro-PET/CT imaging was performed in animal models of acute steatohepatitis (n = 7) and control (n = 7) mice. Results: [3H]proline uptake was 5-fold higher in the HSCs of steatohepatitis rats than controls after incubation of up to 60 min. There was an excellent correlation between [3H]proline uptake and liver collagen expression (r-value > 0.90, p < 0.05). Subsequent liver tissue studies demonstrated 2–3-fold higher proline transporter expression in acute steatohepatitis animals than in controls, and proline-related collagen synthesis was blocked by this transporter inhibitor. In vivo micro-PET/CT studies with [18F]fluoro-proline showed 2–3-fold higher uptake in the livers of acute steatohepatitis mice than in controls. There was an excellent correlation between [18F]fluoro-proline uptake and liver collagen expression in the livers of acute steatohepatitis mice (r-value = 0.97, p < 0.001). Conclusion: [18F]fluoro-proline localizes in the liver and correlates with collagenogenesis in acute steatohepatitis with a signal intensity that is sufficiently high to allow imaging with micro-PET/CT. Thus, [18F]fluoro-proline could serve as a PET imaging biomarker for detecting early-stage liver fibrosis.

1496 Objectives: A room size PET scanner with head tracking will enable investigation of the brain function of active human subjects in a natural setting. The geometric sensitivity of such a scanner at the center of the field of view (FOV) has been previously studied. The purpose of this work is to characterize the geometric sensitivity of a room PET scanner throughout the entire FOV. Methods: An analytic expression for spatial-dependent geometric sensitivity was derived for the case of a rectangular room with PET detectors along each of the walls. The detectors are at the same distance above the floor and their height is the same, thus forming an open box configuration. For a point source at an arbitrary location in the PET FOV the probability of escape of one or both annihilation photons through the top or bottom bounding planes of the PET detector box is modeled. The sensitivity expression has 12 terms and uses formulae for the solid angle of right square pyramids. The derived expression will apply to any open box arrangement of PET detectors. As an application, sensitivity maps were calculated for a square room with dimensions 3 m on a side, and for detectors with heights of 1 and 2 m. Representative linear profiles through the FOV were generated and compared. Results: Geometric sensitivities from the derived equation agree with values from limiting cases, such as for points on the central axis of the PET FOV. In horizontal slices parallel to the floor, sensitivity in central planes is peaked at the center of the FOV. In horizontal slices closer to the top and bottom of the detectors, sensitivity decreases near the center of the FOV and increases toward the walls of the room. In vertical slices parallel to the walls the sensitivity profiles have a triangular shape at the center of the FOV and approximate a triangular shape closer to the walls. This is similar to the triangular sensitivity profile along the central axis of a conventional cylindrical PET scanner. Geometric sensitivity increases with the height of the detectors, as expected, and the sensitivity maps show similar features for different detector heights. Conclusions: An analytic expression was developed for the 3D spatial-dependent geometric sensitivity of a rectangular room PET scanner. The formula will apply to any open box arrangement of PET detectors. Application of the expression provides insight into the sensitivity function of a room PET system and is useful in system design.

An increasing number of extremely obese patients (BMI > 40 kg/m 2 ) undergo PET myocardial perfusion imaging (MPI), posing great demands for accurate activity quantitation. An ultra-large anthropomorphic cardiac-torso phantom was custom built to study this case. The phantom was loaded with F-18 with organ concentrations modeling a Rb-82 MPI study. Transmural and 50% transmural defects were placed in the cardiac insert. The phantom was imaged on a TOF PET/CT scanner using clinical acquisition and image reconstruction protocols. Some truncation and streak artifacts were observed on the x-ray CT scan used for attenuation and scatter correction. Myocardial activity appeared relatively uniform and the defects were easily seen in short axis heart slices. Cardiac segments not containing defects showed good uniformity and had normalized perfusion values > 85% of the peak segmental value. An ultra-large anthropomorphic torso phantom is valuable to model Rb-82 myocardial perfusion studies of extremely obese patients.

Postischemic adaptation results in characteristic myocardial structural and functional changes in the ventricular tachycardia (VT) substrate. The aim of this study was to compare myocardial structural and functional adaptations (late gadolinium enhancement/abnormal innervation) with detailed VT mapping data to identify regional heterogeneities in postischemic changes. Methods: Fifteen patients with ischemic cardiomyopathy and drug-refractory VT underwent late gadolinium enhancement cardiac MRI (CMR), 123I-metaiodobenzylguanidine SPECT, and high-resolution bipolar voltage mapping to assess fibrosis (>3 SDs), abnormal innervation (<50% tracer uptake), and low-voltage area (<1.5 mV), respectively. Three-dimensional reconstructed CMR/123I-metaiodobenzylguanidine models were coregistered for further comparison. Results: Postischemic structural and functional adaptations in all 3 categories were similar in size (reported as median [quartile 1-quartile 3]: CMR scar, 46.1 cm2 [33.1-86.9 cm2]; abnormal innervation, 47.8 cm2 [40.5-68.1 cm2]; and low-voltage area, 29.5 cm2 [24.5-102.6 cm2]; P > 0.05). However, any single modality underestimated the total VT substrate area defined as abnormal in at least 1 of the 3 modalities (76.0 cm2 [57.9-143.2 cm2]; P < 0.001). Within the total VT substrate area, regions abnormal in all 3 modalities were most common (25.2%). However, significant parts of the VT substrate had undergone heterogeneous adaptation (abnormal in <3 modalities); the most common categories were "abnormal innervation only" (18.2%), "CMR scar plus abnormal innervation only" (14.9%), and "CMR scar only" (14.6%). All 14 VT channel/exit sites (0.88 ± 0.74 mV) were localized to myocardium demonstrating CMR scar and abnormal innervation. This specific tissue category accounted for 68.3% of the CMR scar and 31.2% of the total abnormal postischemic VT substrate area. Conclusion: Structural and functional imaging demonstrated regional heterogeneities in the postischemic VT substrate not appreciated by any single modality alone. The coexistence of abnormal innervation and CMR scar may identify a particularly "proarrhythmic" adaptation and may represent a potential novel target for VT ablation.

PurposeApplication of advanced imaging techniques, such as PET and x ray CT, can potentially improve detection of breast cancer. Unfortunately, both modalities have challenges in the detection of some lesions. The combination of the two techniques, however, could potentially lead to an overall improvement in diagnostic breast imaging. The purpose of this investigation is to test the basic performance of a new dedicated breast-PET/CT. MethodsThe PET component consists of a rotating pair of detectors. Its performance was evaluated using the NEMA NU4-2008 protocols. The CT component utilizes a pulsed x ray source and flat panel detector mounted on the same gantry as the PET scanner. Its performance was assessed using specialized phantoms. The radiation dose to a breast during CT imaging was explored by the measurement of free-in-air kerma and air kerma measured at the center of a 16 cm-diameter PMMA cylinder. Finally, the combined capabilities of the system were demonstrated by imaging of a micro-hot-rod phantom. ResultsOverall, performance of the PET component is comparable to many pre-clinical and other dedicated breast-PET scanners. Its spatial resolution is 2.2 mm, 5 mm from the center of the scanner using images created with the single-sliced-filtered-backprojection algorithm. Peak NECR is 24.6 kcps; peak sensitivity is 1.36%; the scatter fraction is 27%. Spatial resolution of the CT scanner is 1.1 lp/mm at 10% MTF. The free-in-air kerma is 2.33 mGy, while the PMMA-air kerma is 1.24 mGy. Finally, combined imaging of a micro-hot-rod phantom illustrated the potential utility of the dual-modality images produced by the system. ConclusionThe basic performance characteristics of a new dedicated breast-PET/CT scanner are good, demonstrating that its performance is similar to current dedicated PET and CT scanners. The potential value of this system is the capability to produce combined duality-modality images that could improve detection of breast disease. The next stage in development of this system is testing with more advanced phantoms and human subjects.

The effect of time-of-flight (TOF) and point spread function (PSF) modeling in image reconstruction has not been well studied for cardiac PET. This study assesses their separate and combined influence on 82Rb myocardial perfusion imaging in obese patients.

267 Objectives: Early-stage liver fibrosis (LF), associated with Alcoholic liver disease (ALD), is potentially reversible, but difficult to detect and quantify. In this study we evaluated the application of a positron emitting radiofluorinated analog of the proline amino acid, 18F-FP, as a potential novel approach to early-stage LF detection, in vivo. Uptake of 18F-FP by activated hepatic stellate cells (HSCs) was quantified as a surrogate of collagenogenesis in an early-stage LF model. Methods: For in vivo studies, we quantified the normal 18F-FP uptake in liver using PET/CT imaging in controls and traced the 18F-FP biodistribution over time in different organs. Static 18F-FP PET/CT imaging was then used to trace 18F-FP uptake in the liver in the setting of early-stage LF compared to 18F-FP uptake in normal liver. Early-stage LF was confirmed by histopathology, blood chemistry, and clinical factors. High 18F-FP purity was confirmed prior to each experiment by HPLC. 18F-NaF PET/CT was performed concurrently and the biodistribution was compared to 18F-FP as a control for free 18F. Findings were correlated with collagen gene expression. Results: In vivo,18F-FP uptake in early-stage LF was optimally imaged during a 60-150 minute imaging period. There was minimal fibrosis in ASH mice, but no difference in HA and alpha 2M (A2M). However, quantification of 18F-FP uptake using % of injected dose (ID), nCi/cc and standardized uptake values (SUVs) demonstrated liver uptake of 18F-FP in early-stage LF was 2-3 times that of controls, and strongly correlated with liver collagen expression (r = 0.97), which was statistically significant (p Conclusions: 18F-FP PET/CT imaging can distinguish increased liver proline uptake in early-stage LF, in vivo, before chemical biomarkers. These resultssuggest promise as a novel non-invasive diagnostic tool to detect early-stage LF in patients with ALD.

Cardiovascular positron emission tomography (PET) imaging provides high-quality visual and quantitative myocardial perfusion and function images. In addition, cardiovascular PET can assess myocardial viability, myocardial inflammatory disorders such as cardiac sarcoid, and infections of implanted devices including pacemakers, ventricular assist devices, and prosthetic heart valves. As with all nuclear cardiology procedures, the benefits need to be considered in relation to the risks of exposure to radiation. When performed properly, these assessments can be obtained while simultaneously minimizing radiation exposure. The purpose of this information statement is to present current concepts to minimize patient and staff radiation exposure while ensuring high image quality.