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Objective. Manual analysis of individual cancer lesions to assess disease response is clinically impractical and requires automated lesion tracking methodologies. However, no methodology has been developed for whole-body individual lesion tracking, across an arbitrary number of scans, and acquired with various imaging modalities. Approach. This study introduces a lesion tracking methodology and benchmarked it using 23 68Ga-DOTATATE PET/CT and PET/MR images of eight neuroendocrine tumor patients. The methodology consists of six steps: (1) alignment of multiple scans via image registration, (2) body-part labeling, (3) automatic lesion-wise dilation, (4) clustering of lesions based on local lesion shape metrics, (5) assignment of lesion tracks, and (6) output of a lesion graph. Registration performance was evaluated via landmark distance, lesion matching accuracy was evaluated between each image pair, and lesion tracking accuracy was evaluated via identical track ratio. Sensitivity studies were performed to evaluate the impact of lesion dilation (fixed versus automatic dilation), anatomic location, image modalities (inter- versus intra-modality), registration mode (direct versus indirect registration), and track size (number of time-points and lesions) on lesion matching and tracking performance. Main results. Manual contouring yielded 956 lesions, 1570 lesion-matching decisions, and 493 lesion tracks. The median residual registration error was 2.5 mm. The automatic lesion dilation led to 0.90 overall lesion matching accuracy, and an 88% identical track ratio. The methodology is robust regarding anatomic locations, image modalities, and registration modes. The number of scans had a moderate negative impact on the identical track ratio (94% for 2 scans, 91% for 3 scans, and 81% for 4 scans). The number of lesions substantially impacted the identical track ratio (93% for 2 nodes versus 54% for ≥5 nodes). Significance. The developed methodology resulted in high lesion-matching accuracy and enables automated lesion tracking in PET/CT and PET/MR. [ABSTRACT FROM AUTHOR]

Abstract: To develop a protocol for prevention of hepatitis B virus (HBV) transmission in Wisconsin prisons, we interviewed 619 male prisoners at incarceration to obtain information on hepatitis B risk factors. We defined previous infections by the presence of hepatitis B surface antigen (HBsAg), antibody 10 hepatitis B surface antigen (anti-HBs), or antibody to hepatitis B core antigen (anti-HBc). Logistic regression was used to develop a model of relative risk (RR) of HBV infection. Use of illicit intravenous (IV)drugs was the most important risk factor because of a high prevalence of IV drug use and an RR which ranged from 2.93-7.47. Other important risk factors were: prior hepatitis or jaundice IRR = 6.28), race (RR = 2.54 for Blacks, RR = 3.28 for Latinos), transfusion (RR = 3.00). and age. Previous imprisonment was not an independent risk factor for HBV, hence selective serologic screening and vaccination of prisoners are justified rather than mass screening and vaccination Based upon prevalence of hepatitis B markers in subgroups, it is necessary to screen prisoners with prior hepatitis or jaundice, prior transfusion, and users of IV drugs. The identification of HBsAg carriers by such screening could prevent infection of "household" contacts. Users of IV drugs who are susceptible to HBV infection should be vaccinated. The remaining prisoners constitute a low-risk group for HBV infection and do nut require serologic screening or vaccination. (Am J Public Health 1985:75:1182-1185.) [ABSTRACT FROM AUTHOR]

Positron emission tomography with fluorine-18-deoxyglucose (FDG-PET) detects active lymphoid tissues during HIV-1 infection in man. We used FDG-PET to study anatomical correlates of HIV-1 infection in man. Whole-body FDG-PET images from 15 patients with HIV-1 showed distinct lymphoid tissue activation in the head and neck during acute disease, a generalised pattern of peripheral lymph-node activation at mid-stages, and involvement of abdominal lymph nodes during late disease. Unexpectedly, HIV-1 progression was evident by distinct anatomical correlates, suggesting that lymphoid tissues are engaged in a predictable sequence. Understanding the anatomy of HIV-1 infection could encourage use of surgical or radiological interventions to supplement chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The clinical utility of positron emission tomography/computed tomography (PET/CT) in comparison to standard workup in patients with known or suspected inflammatory bowel disease (IBD) is unknown.Procedures: Clinical data were collected on seven patients with known or suspected IBD undergoing PET/CT. Standard workup included history, physical exam, laboratory tests, colonoscopy and/or cross-sectional imaging. We divided the intestine into five regions [small bowel and four colon (ascending, transverse, descending and rectosigmoid)] and graded relative standard uptake values 0, 1, 2 or 3 by comparison to the liver, using a region-of-interest analysis (0 = no activity, 1 = liver, 2 and 3 = significant inflammation).Results: In patients 1 and 2, PET/CT demonstrated more activity than we thought clinically present. The other patients avoided unnecessary escalation or initiation of IBD therapy based on PET/CT results. Compared with standard workup, all seven patients had superior results when therapeutic decisions were based on PET/CT.Conclusions: We found PET/CT to be very useful in diagnosis and management in patients with known or suspected IBD. [ABSTRACT FROM AUTHOR]

Abstract: Assessment of treatment response in acute leukemia is routinely performed after therapy via bone marrow biopsy. We investigated the use of positron emission tomography (PET) for early assessment of treatment response in patients with acute myeloid leukemia (AML), using the proliferation marker 3′-deoxy-3′-[18F]fluoro-l-thymidine (FLT). Eight adult AML patients receiving induction chemotherapy underwent whole-body FLT PET/CT scans acquired at different time points during therapy. Patients who entered complete remission (CR) exhibited significantly lower FLT uptake in bone marrow than those patients with resistant disease (RD). In bone marrow, mean and maximum standardized uptake values were 0.8, 3.6 for CR and 1.6, 11.4 for RD, p <0.001. FLT PET results for CR and RD patients were independent of assessment time point, suggesting that FLT PET scans acquired as early as 2 days after chemotherapy initiation may be predictive of clinical response. This pilot study suggests that FLT PET imaging during induction chemotherapy may serve as an early biomarker of treatment response in AML. [Copyright &y& Elsevier]

Purpose: Accurate staging of esophageal cancer (ECA) is critical in determining appropriate therapy. Endoscopic ultrasound (EUS), computed tomography (CT) and positron emission tomography (PET) scanning can be used, but limited data exists regarding the use of combined PET/CT fusion imaging and EUS in ECA staging. The objective of this study is to evaluate the role of integrated PET/CT imaging and EUS in the staging of ECA.Procedures: Identification of patients diagnosed with ECA from 2004 to 2007 that underwent staging PET/CT and EUS. Data regarding tumor detection, lymph node identification, presence of metastatic disease, and affect on patient management were collected and compared between PET/CT and EUS.Results: Eighty-one patients (65 male, 16 female) were identified with mean age of 63.5 years who underwent EUS and PET/CT to stage known ECA. PET/CT identified the primary tumor in 74/81 (91.4%) of cases, compared to 81/81 (100%) with EUS. Locoregional adenopathy was seen by PET/CT in 29/81 (35.8%) of cases, compared to 49/81 (60.5%) by EUS (p = 0.0001). PET/CT identified celiac axis adenopathy in 8/81 (9.9%) of cases, compared to 11/81 (13.6%) with EUS (p = 0.5050). PET/CT identified 17/81 (21.0%) of patients with distant metastases who subsequently did not undergo attempt at curative surgical resection.Conclusions: In ECA, EUS is superior to PET/CT for T staging and in identifying locoregional nodes, while PET/CT provides M staging. EUS and integrated PET/CT appear to independently affect treatment decisions, indicating complimentary and necessary roles in the staging of ECA. [ABSTRACT FROM AUTHOR]

Purpose: There is a continuous search for imaging techniques with high sensitivity and specificity for brain tumors. Positron emission tomography (PET) imaging has shown promise, though many PET agents either have a low tumor specificity or impractical physical half-lives. [124I]CLR1404 is a small molecule alkylphosphocholine analogue that is thought to bind to plasma membrane lipid rafts and has shown high tumor-to-background ratios (TBR) in a previous pilot study in brain tumor patients. This study attempts to define the clinical value of [124I]CLR1404 PET/CT (aka CLR124).Procedures: Adult patients with new or suspected recurrence of high-grade primary or metastatic brain tumors (N = 27) were injected with [124I]CLR1404 followed by PET/CT at 6, 24, and 48 h. Standard uptake values (SUV) and TBR values were calculated for all time points. Uptake of [124I]CLR1404 was qualitatively assessed, compared with magnetic resonance imaging (MRI), and correlated with clinical outcome. Final diagnosis (N = 25) was established based on surgically resected tissue or long-term follow-up.Results: Positive uptake with high TBR was detected in all but one patient with a final diagnosis of primary/recurrent brain tumor (12/13) and in less than half of patients with treatment-related changes (5/12). Concordance between [124I]CLR1404 uptake and contrast enhancement on MRI was seen in < 40 %, with no concordance between T2-hyperintensities and uptake. No significant difference in overall outcome was found between patients with and without [124I]CLR1404 uptake.Conclusions: The uptake pattern in these patients suggests a very high sensitivity of [124I]CLR1404 PET/CT for diagnosing tumor tissue; however, tumor specificity needs to be further defined. Relative lack of concordance with standard MRI characteristics suggests that [124I]CLR1404 PET/CT provides additional information about brain tumors compared to MRI alone, potentially improving clinical decision-making. [ABSTRACT FROM AUTHOR]

Purpose: Rapid disease progression associated with increased tumor proliferation has been observed during withdrawal of anti-angiogenic therapy. We characterize the dynamics of withdrawal flare for axitinib.Methods: Thirty patients with metastatic solid malignancies received axitinib for 2 weeks, followed by a 1-week drug holiday. Twenty patients suitable for PET imaging received scans with (18)F-3'deoxy-3'fluoro-L-thymidine (FLT), a marker of proliferation. Plasma VEGF and axitinib pharmacokinetic levels were also assessed at specified time points.Results: During axitinib withdrawal, significant increases in both SUVmax (+22 %; p = 0.006) and SUVmean (+20 %; p = 0.001) were observed. Significant increases relative to peak axitinib concentration were observed at day 2 withdrawal for SUVmax and SUVmean, with no further significant increase from day 2 to day 7 of withdrawal. No significant change in SUVmax or SUVmean was observed during the treatment period, relative to baseline. VEGF concentration significantly increased when on drug (p < 0.001) and decreased back to a level indistinguishable from baseline by day 7 of drug washout (p = 0.448). No correlation between change in VEGF and change in imaging metrics was observed.Conclusions: A significant increase in tumor proliferation was observed during withdrawal of axitinib therapy, and this flare occurred within 2 days of axitinib withdrawal. An exploratory analysis indicated that this flare may be associated with poor clinical outcome. [ABSTRACT FROM AUTHOR]

Intrapulmonary arteriovenous anastomoses (IPAVs) are large diameter connections that allow blood to bypass the lung capillaries and may provide a route for right-to-left embolus transmission. These anastomoses are recruited by exercise and catecholamines and hypoxia. Yet, whether IPAVs are recruited via direct, oxygen sensitive regulatory mechanisms or indirect effects secondary to redistribution pulmonary blood flow is unknown. Here, we hypothesized that the addition of exercise to hypoxic gas breathing, which increases cardiac output, would augment IPAVs recruitment in healthy humans. To test this hypothesis, we measured the transpulmonary passage of 99mTc-macroaggregated albumin particles (99mTc-MAA) in seven healthy volunteers, at rest and with exercise at 85% of volitional max, with normoxic (FIO2 = 0.21) and hypoxic (FIO2 = 0.10) gas breathing. We found increased 99mTc-MAA passage in both exercise conditions and resting hypoxia. However, contrary to our hypothesis, we found the greatest 99mTc-MAA passage with resting hypoxia. As an additional, secondary endpoint, we also noted that the transpulmonary passage of 99mTc-MAA was well-correlated with the alveolar-arterial oxygen difference (A-aDO2) during exercise. While increased cardiac output has been proposed as an important modulator of IPAVs recruitment, we provide evidence that the modulation of blood flow through these pathways is more complex and that increasing cardiac output does not necessarily increase IPAVs recruitment. As we discuss, our data suggest that the resistance downstream of IPAVs is an important determinant of their perfusion. [ABSTRACT FROM AUTHOR]

Abstract: Spatial organization of tumor phenotype is of great interest to radiotherapy target definition and outcome prediction. We characterized tumor phenotype in patients with cancers of the oropharynx through voxel-based correlation of PET images of metabolism, proliferation, and hypoxia. Methods: Patients with oropharyngeal cancer received 18F-fluorodeoxyglucose (FDG) PET/CT, 18F-fluorothymidine (FLT) PET/CT, and 61Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) PET/CT. Images were co-registered and standardized uptake values (SUV) were calculated for all modalities. Voxel-based correlation was evaluated with Pearson’s correlation coefficient in tumor regions. Additionally, sensitivity studies were performed to quantify the effects of image segmentation, registration, noise, and segmentation on R. Results: On average, FDG PET and FLT PET images were most highly correlated (R FDG:FLT =0.76, range 0.53–0.85), while Cu-ATSM PET showed greater heterogeneity in correlation to other tracers (R FDG:Cu-ATSM =0.64, range 0.51–0.79; R FLT:Cu-ATSM =0.61, range 0.21–0.80). Of the tested parameters, correlation was most sensitive to image registration. Misregistration of one voxel lead to ΔR FDG =0.25, ΔR FLT =0.39, and ΔR Cu-ATSM =0.27. Image noise and reconstruction also had quantitative effects on correlation. No significant quantitative differences were found between GTV, expanded GTV, or CTV regions. Conclusions: Voxel-based correlation represents a first step into understanding spatial organization of tumor phenotype. These results have implications for radiotherapy target definition and provide a framework to test outcome prediction based on pretherapy distribution of phenotype. [Copyright &y& Elsevier]

Abstract: Objectives: The goals of this work were (1) to determine the effect of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, and EEG on the decision to perform temporal lobe epilepsy (TLE) surgery, and (2) to determine if FDG-PET, MRI, or EEG predicts surgical outcome. Methods: All PET scans ordered (2000–2010) for epilepsy or seizures were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, κ statistics, univariate analysis, and logistic regression. Results: Of the 186 patients who underwent FDG-PET, 124 had TLE, 50 were surgical candidates, and 34 had surgery with post-operative follow-up. Median length of follow-up was 24months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy (P <0.001) with odds ratios of 42.8, 20.4, and 6.3, respectively. FDG-PET was the only significant predictor of postoperative outcome (P <0.01). Conclusion: MRI showed a trend toward having the most influence on surgical candidacy, but only FDG-PET predicted surgical outcome. [Copyright &y& Elsevier]

Purpose: The purpose of this study was to evaluate the appropriate 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography (FDG-PET) determination in patients with inflammatory bowel disease (IBD) before and after clinical improvement to see if this determination correlates with clinical activity.Procedures: We performed PET-computed tomography (PET/CT) on five patients before and after successful medical therapy in patients with moderately active IBD. Each patient had five bowel segments scored (0-3) for the appropriate FDG-PET determination.Results: There were five patients [Crohn's disease (CD) = 3, ulcerative colitis = 2] who were studied an average of 437 days (range, 77-807) after initial PET/CT scan. All patients showed significant improvement in physician global assessment scores (p = 0.004) and underwent repeat PET/CT. The total score of all segments was 32 pretreatment and 14 posttreatment (p < 0.01). Of 11 pretreatment active segments, nine (82%) segments either became inactive or displayed decreased activity, while two showed no change (p < 0.001).Conclusion: Appropriate FDG-PET determination decreases with successful treatment of inflammation in active IBD and correlates with symptom improvement. [ABSTRACT FROM AUTHOR]