Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that [15O]-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.

Purpose To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). Methods and Materials Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. Results The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. Conclusions This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

The antibody 3F8, an IgG3 murine monoclonal antibody (MoAb) against disialoganglioside GD2, could target iodine-131 (131I) to established subcutaneous human neuroblastoma (NB) xenografts in BALB/c nude mice. 131I-radiolabeled MoAb (0.125-1 mCi) was injected iv. Tumor radioactivity over time was calculated from scintigraphy, and radiation dose to individual tumors was calculated. Tumor shrinkage occurred only with 131I-labeled 3F8, but not with nonradioactive 3F8 or radiolabeled irrelevant antibody. While the tumor of the control mice enlarged by tenfold, the treated tumor showed over 95% shrinkage by 12 days. Both the rate of shrinkage and duration of tumor response were dose dependent. Calculated doses of more than 10,000 rad could be achieved. Only those tumors that received more than 4,200 rad were completely ablated without recurrence. Recurrent tumors were not antigen negative or radioresistant. These results confirmed the prediction based on imaging studies that human NB xenografts could be effectively eradicated with the use of 131I-labeled MoAb 3F8 with tolerable toxicities.

The mathematical models used to analyze positron emission tomography (PET) data obtained for receptor quantitation have many unknown parameters which must be estimated from the data. Obtaining unique and precise estimates of the model parameters from PET data is difficult as a result of the complex interdependence of the parameters. Here the authors address the task of estimating the concentration of myocardial beta-adrenergic receptors using unlabeled and (18)F-labeled S(-)-fluorocarazolol as the receptor ligand. For a three-injection study the authors have optimized the ligand injection times and dosages using the D-optimal criterion for estimating receptor concentration. They found that in optimizing a three-injection experimental design, the dose of ligand in the third injection approaches zero so that the optimal three-injection design is actually a two-injection experiment. Using this optimal experiment, the authors demonstrate estimates of receptor concentration that are almost five times as precise as compared to an empirically designed three-injection experiment.

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To estimate in vivo myocardial beta-adrenergic receptor concentration with sufficient precision and to reduce the experimental complexities in positron emission tomography (PET), an iterative optimal design method is applied. An initial three-injection protocol, utilising [F-18]-labelled (R)- and (S)-fluorocarazolol and unlabelled (S)-fluorocarazolol, is optimised for ligand dosages and administration times to maximise the precision of all model parameters using the D-optimal criterion. Using this experimental protocol, PET data are collected in porcine studies, and model parameters are estimated. All model parameters are identified with satisfactory precision. The in vivo myocardial beta-receptor concentration is 7.5+/-0.6 pmol x ml(-1), which corresponds to the in vitro result of 10.1+/-1.3 pmol x ml(-1). With more accurate parameter values, a simplified two-injection protocol is optimally designed, utilising only radiolabelled and unlabelled (S)-fluorocarazolol, based on a new criterion to maximise the precision of the beta-receptor concentration. This revised optimum design predicts that the in vivo beta-receptor concentration can be estimated with good precision but reduced experiment complexity.

Gamma scintigraphy is often used to quantify deposition patterns from aerosol inhalers. The errors caused by scatter and tissue attenuation in planar Tc-99m gamma scintigraphy were investigated based on the data collected from four subjects in this study. Several error correction methods were tested. The results from two scatter correction methods, Jaszczak's method and factor analysis of dynamic sequences (FADS), were similar. Scatter accounted for 20% of raw data in the whole lung, 20% in the oropharynx, and 43% in the central airways and esophagus. Three attenuation correction methods were investigated and compared. These were: uniform attenuation correction (UAC), a known method used for inhalation drug imaging work; the broad-beam attenuation correction used for organ imaging in nuclear medicine; and a narrow-beam inhomogeneous tissue attenuation correction proposed in this study. The three methods differed significantly (p < 0.05), but all indicated that attenuation is a severe quantification problem. The narrow beam attenuation correction with scatter correction, showed that raw data underestimated tracer deposition by 44% in the lung, 137% in the oropharynx, and 153% in the trachea/esophageal region. To quantify aerosol lung deposition using planar scintigraphy even in relative terms, corrections are necessary. Much of the literature concerning quantified aerosol dose distributions measured by gamma scintigraphy needs to be interpreted carefully.

The widespread prevalence of atherosclerotic vascular disease has given rise to the need for a simple, noninvasive imaging examination.Present-day technologies aimed at solving this problem are either error prone, invasive, or lacking in universal applicability. The potential of MR to quantitate flow has been explored for more than 30 years in the laboratory setting and has been addressed in other communications [1][2][3][4][5][6][7][8][9][10][11][12][13]. More recent advances in the techniques collectively known as magnetic resonance angiography (MRA) represent significant progress toward achieving the goal of a noninvasive vascular examination.MRA is a generic term describing numerous imaging techniques that visualize vascular lumen morphology through MR signal changes resulting from time-of-flight phenomena and/ or phase shifts caused by motion along imaging gradients. Although blood-flow measurement and direct atherosclerotic plaque identification and analysis are of pathophysiologic and diagnostic interest, we believe that angiography-like techniques remain the most useful methods of detecting remedial vascular lesions. This paper will summarize the pertinent theory and previous research efforts, analyze the current status of clinical research, and attempt to project future directions of MRA. A glossary is included to clarify terminology that is peculiar to MRA and that may be unfamiliar to the reader. Background