Karl F. Hubner

Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment.

Brain imaging studies of early Alzheimers disease (AD) have shown decreased metabolism predominantly in the posterior cingulate cortex (PCC), medial temporal lobe, and inferior parietal lobe. This study investigated functional connectivity between these regions, as well as connectivity between these regions and the whole brain.

An Assessment of the Impact of Incorporating Time-of-Flight Information into Clinical PET/CT Imaging

The introduction of fast scintillators with good stopping power for 511-keV photons has renewed interest in time-of-flight (TOF) PET. The ability to measure the difference between the arrival times of a pair of photons originating from positron annihilation improves the image signal-to-noise ratio (SNR). The level of improvement depends upon the extent and distribution of the positron activity and the time resolution of the PET scanner. While specific estimates can be made for phantom imaging, the impact of TOF PET is more difficult to quantify in clinical situations. The results presented here quantify the benefit of TOF in a challenging phantom experiment and then assess both qualitatively and quantitatively the impact of incorporating TOF information into the reconstruction of clinical studies. A clear correlation between patient body mass index and gain in SNR was observed in this study involving 100 oncology patient studies, with a gain due to TOF ranging from 1.1 to 1.8, which is consistent with the 590-ps time resolution of the TOF PET scanner. The visual comparison of TOF and non-TOF images performed by two nuclear medicine physicians confirmed the advantages of incorporating TOF into the reconstruction, advantages that include better definition of small lesions and image details, improved uniformity, and noise reduction.

Differentiating benign from malignant lung lesions using quantitative parameters of FDG PET images

UNLABELLED Fluorine-18 labeled deoxyglucose positron-emission tomography (FDG-PET) applications in oncology include the differential diagnosis of chest masses and single pulmonary nodules. However, FDG is not tumor-specific; rather, it also accumulates in inflammatory processes. This study was performed to identify image parameters that would improve the specificity of PET. METHODS Twenty-six patients who had benign and malignant lung lesions were examined retrospectively. Positron-emission tomography data were acquired in dynamic scanning mode after intravenous bolus of 250-402 MBq of FDG. Standardized uptake values (SUVs) were calculated and Patlak analyses were performed in selected regions of interest in the PET images. Positron-emission tomography results were related to histological diagnosis (N = 49) or clinical follow-up (N = 3). RESULTS The specificity and sensitivity of the original PET scan reports, which was based on visual image interpretation and loosely applied SUVs, was 100% and 73%, respectively. Using the SUVs with a cut-off value of 3.8 and Kpat value with a cut-off at 0.025 min-1 improved the specificity to 81% and 85%. CONCLUSION FDG-PET image interpretation can be facilitated by using SUV information or the accumulation rate of the radiotracer (Patlak). With additional validation, this method could have a significant cost-effective impact on the medical/surgical management of chest masses.

Time Course of Early Response to Chemotherapy in Non–Small Cell Lung Cancer Patients with 18F-FDG PET/CT

PET and 18F-FDG have the potential to follow the early metabolic response to chemotherapy in patients with non–small cell lung cancer and to predict success or failure of the therapy. Methods: We studied 16 patients with non–small cell lung cancer as they followed 2 courses of docetaxel and carboplatin. Each patient was studied weekly for 7 wk, and tissue activity was assessed by the amount of radioactivity retained 90 min after the intravenous injection of 18F-FDG. In a prospective analysis, the linear least-squares method was used to evaluate the time course of metabolic activity in tumor and liver, bone marrow, and unaffected lung tissues; a metabolic response was defined as a response in which the slope of the regression was negative and significantly different from zero. Our hypothesis was that patients who exhibited a tumor metabolic response would survive longer than those who did not. In a retrospective examination of our data, we grouped our patients into those who survived <6 mo and those who survived longer and calculated the difference in the standardized uptake value (SUV) between day 7 and subsequent time points to determine the most appropriate timing of 2 PET studies in predicting response to therapy. Results: Fifteen of 16 patients completed the study. In the prospective study, 8 patients were classified as nonresponders as the slope of the regression of tumor SUV versus time was not different from zero; they all died within 35 wk of the end of their study. Seven patients were classified as responders; 5 survived and 2 died, one at 25 wk and the other at 76 wk. In the retrospective study, a decrease of 0.5 SUV between studies performed at 1 and 3 wk after the initiation of chemotherapy was predictive of those patients who survived >6 mo and in whom chemotherapy was presumably successful. Conclusion: Patients with non–small cell lung cancer who had a positive outcome, as exhibited by prolonged survival, were those who showed a tumor metabolic response assessed using weekly 18F-FDG PET studies. 18F-FDG PET studies performed at 1 and 3 wk after the initiation of chemotherapy allowed prediction of the response to therapy.

Characterization of chest masses by FDG positron emission tomography

Radiographic imaging techniques have proved to be of limited value in characterizing chest masses. Likewise, scintigraphic techniques with tumor-seeking single photon emitting agents have shown marginal practical benefit. In contrast, high resolution PET with [F-18]-2-fluoro-2-D-deoxyglucose (FDG) offers a unique opportunity to distinguish benign from malignant processes by determining metabolic characteristics. PET scan results, including graphical analysis of tumor transfer constants (Patiak plot) in 21 patients with primary lung cancer, were compared to clinical outcome (histologic proof or clinical follow-up of longer than 1 year) in 54 patients who had chest masses identified by CT and/or plain film. The patients were categorized into three groups. The first group (N = 23) had primary, unknown, lung masses. Differentiation of benign from malignant tumors by PET had a sensitivity of 100% and a specificity of 67%. The second group (N = 13) had proven lung carcinoma or lymphoma and post-therapy PET scanning for recurrent tumor. In this setting, PET had a sensitivity of 83% and a specificity of 80%. The third group (N = 18) had extrathoracic malignancies and suspected pulmonary metastases. Metastatic lesions were Identified with a sensitivity of 87% and specificity of 83%. Glucose uptake by normal tissue is variable and inflammatory/infectious processes can have high FDG uptake and overlap with the glucose uptake of malignant tissue. FDG PET is useful in characterizing chest tumors based on the level of their metabolic activity. Malignant tissue has a high glucose uptake. Elevated FDG uptake by an active inflammatory process may produce overlapping results. Despite this shortcoming, PET can help to separate benign from most malignant lung lesions, to confirm lung metastases, and to monitor the therapy of chest neoplasms.

Increased F-18 FDG accumulation in an acute fracture

Markedly increased FDG uptake was noted in a 2-week-old fracture of the clavicle and scapula in a 24-year-old man. This finding emphasizes the need to consider benign etiologies such as trauma for focally increased FDG accumulation in bone.

The Potential of F-18-FDG PET in Breast Cancer: Detection of Primary Lesions, Axillary Lymph Node Metastases, or Distant Metastases

This retrospective study was done to evaluate the utility of 2-[F-18]fluoro-2-deoxy-D-glucose positron emission tomography (F-18-FDG PET) in identifying primary and recurrent breast cancer and lymph node metastases. One hundred whole-body PET scans of 87 patients were reviewed. PET results obtained with F-18-FDG and an ECAT/EXACT-921 or an ECAT-931 (Siemens/CTI) were based on visual interpretation, or standardized uptake values (SUVs), related to histology and also compared to computerized tomography (CT) and mammography results. The sensitivity for PET in detecting primary (N = 35 studies) and recurrent breast cancer (N = 65 studies) was 96% and 85% with a specificity of 91% and 73%. The sensitivity for lymph node metastases at the time of initial diagnosis was 100% with a specificity of 100%. Quantitative SUV information did not improve the accuracy of F-18-FDG PET in identifying primary breast cancers. The results suggest that whole-body PET is useful in detecting recurrence or metastases, may be useful in detecting lymph node metastases prior to initial axillary lymph node dissection, but is less sensitive in excluding axillary lymph nodes metastases later in the course of the disease.

Cost Analysis of FDG PET for Managing Patients with Ovarian Cancer.

Monte Carlo simulation analysis was used to compare the cost of managing recurrent ovarian cancer patients with and without the use of positron emission tomography (PET) scanning. Assumptions in the management pathway were: (1) a positive PET scan led to either laparoscopy or laparotomy, followed by chemotherapy (true positive PET) or follow-up (false positive PET); (2) a negative PET scan resulted in continued follow-up (true negative PET) or laparotomy (false negative PET); and, (3) a laparotomy led to chemotherapy or follow-up. In this simulation, sensitivity and specificity of FDG PET for recurrent ovarian cancer varied from 72-91% (mean 83%) and 69-95% (mean 85%), respectively, as defined by the ROC curve. Using a prevalence rate of 30% for recurrent ovarian cancer, the mean PET false negative rate was 5%. Thus, when using PET to manage the diagnostic evaluation, the number of unnecessary laparotomies was reduced from 70% to 5%, with 35% of patients undergoing laparoscopy for recurrent disease instead of laparotomy. If laparotomy is used in place of laparoscopy, unnecessary surgery can be avoided in 30% of patients. Costs for procedures were based both on hospital charges, and Medicare reimbursement rates. Cost savings per patient ranged from

Optimizing Imaging Time for Improved Performance in Oncology PET Studies

1,941 to

Sequential Positron Emission Tomographic Evaluations of Brain Metabolism in Acute Herpes Encephalitis

11,766, assuming that follow-up evaluation was similar for both groups. Estimated cost savings were due to the need for fewer surgical procedures when using PET in the diagnostic evaluation, the reimbursement rate scheme employed, and whether laparotomy or laparoscopy was used in the management algorithm for PET positive patients. In conclusion, FDG PET can reduce unnecessary invasive staging procedures and save health care costs when used appropriately in the management of patients with recurrent ovarian cancer.