Impact of reduced k-space acquisition on pathologic detectability for volumetric MR spectroscopic imaging.

PURPOSE: To assess the impact of accelerated acquisitions on the spectral quality of volumetric magnetic resonance spectroscopic imaging (MRSI) and to evaluate their ability in detecting metabolic changes with mild injury. MATERIALS AND METHODS: The implementation of a generalized autocalibrating partially parallel acquisition (GRAPPA) method for a high-resolution whole-brain echo planar SI (3D-EPSI) sequence is first described and the spectral accuracy of the GRAPPA-EPSI method is investigated using lobar and voxel-based analyses for normal subjects and patients with mild traumatic brain injuries (mTBI). The performance of GRAPPA was compared with that of fully encoded EPSI for five datasets collected from normal subjects at the same scanning session, as well as on 45 scans (20 normal subjects and 25 mTBI patients) for which the reduced k-space sampling was simulated. For comparison, a central k-space lower-resolution 3D-EPSI acquisition was also simulated. Differences in individual metabolites and metabolite ratio distributions of the mTBI group relative to those of age-matched control subjects were statistically evaluated using analyses divided into hemispheric brain lobes and tissue types. RESULTS: GRAPPA-EPSI with 16-minute scan time yielded robust and similar results in terms of MRSI quantitation, spectral fitting, and accuracy with that of fully sampled 3D-EPSI acquisitions and was more accurate than central k-space acquisition. Primary findings included high correlations (accuracy of 92.6%) between the GRAPPA and fully sampled results. CONCLUSION: Although the reduced encoding method is associated with lower signal-to-noise ratio (SNR) that impacts the quality of spectral analysis, the use of the parallel imaging method can lead to the same diagnostic outcomes as the fully sampled data when using the sensitivity-limited volumetric MRSI.

A phase I study of a combination of yttrium-90-labeled anti-carcinoembryonic antigen (CEA) antibody and gemcitabine in patients with CEA-producing advanced malignancies.

PURPOSE: To determine the maximum tolerated dose of combined therapy using an yttrium-90-labeled anti-carcinoembryonic antigen (CEA) antibody with gemcitabine in patients with advanced CEA-producing solid tumors. EXPERIMENTAL DESIGN: The chimeric human/murine cT84.66 is an anti-CEA intact IgG1, with high affinity and specificity to CEA. This was given at a fixed yttrium-90-labeled dose of 16.6 mCi/m(2) to subjects who had and an elevated CEA in serum or in tumor by immunohistochemistry. Also required was a tumor that imaged with an (111)In-labeled cT84.66 antibody. Patients were treated with escalating doses of gemcitabine given i.v. over 30 minutes on day 1 and 3 after the infusion of the yttrium-90-labeled antibody. Patients were treated in cohorts of 3. The maximum tolerated dose was determined as the highest level at which no >1 of 6 patients experienced a dose limiting toxicity. RESULTS: A total of 36 patients were enrolled, and all but one had prior systemic therapy. The maximum tolerated dose of gemcitabine in this combination was 150 mg/m(2). Dose limiting toxicities at a gemcitabine dose of 165 mg/m(2) included a grade 3 rash and grade 4 neutropenia. One partial response was seen in a patient with colorectal cancer, and 4 patients had a >50% decrease in baseline CEA levels associated with stable disease. Human antichimeric antibody responses were the primary reason for stopping treatment in 12 patients. CONCLUSIONS: Feasibility of combining gemcitabine with an yttrium-90-labeled anti-CEA antibody is shown with preliminary evidence of clinical response.

A phase I trial of (90)Y-DOTA-anti-CEA chimeric T84.66 (cT84.66) radioimmunotherapy in patients with metastatic CEA-producing malignancies.

PURPOSE/OBJECTIVE: Previous radioimmunotherapy (RIT) clinical trials at this institution with (90)Y-labeled cT84.66 anti-CEA (carcinoembryonic antigen) evaluated the antibody conjugated to diethylenetriaminepentaacetic acid (DTPA). The aim of this phase I therapy trial was to evaluate cT84.66 conjugated to the macrocyclic chelate (90)Y-DOTA and labeled with (90)Y in a comparable patient population. EXPERIMENTAL DESIGN: Patients with metastatic CEA-producing cancers were entered in this trial. If antibody targeting to tumor was observed after the administration of (111)In-DTPA cT84.66, the patient then received the therapy infusion of (90)Y-DOTA-cT84.66 1 week later. Serial nuclear scans, blood and urine collections, and computed tomography (CT) scans were performed to assess antibody biodistribution, pharmacokinetics, toxicities, and antitumor effects. RESULTS: Thirteen (13) patients were treated in this study. Dose-limiting hematologic toxicity was experienced at initial starting activity levels of 12 and 8 mCi/m(2). Subsequent patients received systemic Ca-DTPA at 125 mg/m(2) every 12 hours for 3 days post-therapy to allow for a dose escalation to 16 mCi/m(2), where hematologic toxicity was observed with an associated maximum tolerated dose (MTD) of 13.4 mCi/m(2). Tumor doses ranged from 4.4 to 569 cGy/mCi, which translated to 97-12,500 cGy after a single infusion of (90)Y-DOTA-cT84.66. Human anti-chimeric antibody (HACA) response developed in 8 of 13 patients and prevented additional therapy in 4 patients. CONCLUSIONS: This study demonstrates the feasibility of using (90)Y-DOTA-cT84.66 for antibody-guided radiation therapy. Immunogenicity of the DOTA-conjugated cT84.66 antibody was not appreciably greater than that observed with (90)Y-DTPA-cT84.66 in previous trials. Dose-limiting hematopoietic toxicity with (90)Y-DOTA-cT84.66 decreased with Ca-DTPA infusions post-therapy and appears to be comparable to previously published results for (90)Y-DTPA-cT84.66. The highest antibody uptake and tumor doses were to small nodal lesions, which supports the predictions from preclinical and clinical data that RIT may be best applied in the minimal tumor burden setting.

Threshold behavior in electron-transfer collisions between rubidium atoms and C2F5Cl or C2F5I molecules.

Rubidium atoms are accelerated in a high-temperature expansion of hydrogen to produce beams with energies high enough to observe collisional ionization with a cross beam. The speed of the atoms is directly measured by time-of-flight techniques, and the positive and negative ions produced are detected in separate mass spectrometers and detected in coincidence. Chloroperfluoroethane produces C(2)F(5)(-) and Cl(-) ions, whereas iodoperfluoroethane produces I(-), C(2)F(5)(-), and C(2)F(5)I(-) ions. When the measured speed distributions are used, the signal versus energy may be deconvolved to yield thresholds and electron affinities (EAs). The EA for C(2)F(5)I is measured to be 0.96 +/- 0.1 eV. Anomalously high EA values result for C(2)F(5) apparently because C(2)F(5)(-) is produced by parts per million concentrations of Rb(2).

T2-weighted spine imaging with a fast three-point dixon technique: comparison with chemical shift selective fat suppression.

PURPOSE: To develop a phased-array coil-compatible, fast three-point Dixon (TPD) technique, and compare its performance in T2-weighted spine imaging with that of the standard chemical shift selective (CHESS) fat suppression technique. MATERIALS AND METHODS: We acquired T2-weighted spine images of 27 patients using essentially identical scanning parameters with the fast TPD technique and standard fast spin echo (FSE) with CHESS fat suppression. A phased-array coil-compatible image reconstruction algorithm was developed to generate separate water and fat images from the data acquired with the fast TPD technique. Three neuroradiologists independently scored the images from the two different techniques for uniformity of fat suppression and lesion conspicuity using a four-point system (1 = poor, 2 = fair, 3 = good, 4 = best). RESULTS: The reviewers' mean scores were 3.2 and 2.1 for the uniformity of fat suppression, and 3.0 and 2.0 for the lesion conspicuity for the fast TPD and the CHESS fat suppression techniques, respectively. The fast TPD technique was statistically superior to the CHESS technique at P < 0.0005. CONCLUSION: The fast TPD technique provides superior fat suppression and lesion conspicuity, and potentially can be used as an alternative to T2-weighted imaging of the spine.