Faculty Bibliography

In classical mechanics, the system of two coupled harmonic oscillators is shown to possess the symmetry of the Lorentz group O(3,3) or SL(4,r) in the four-dimensional phase space. In quantum mechanics, the symmetry is reduced to that of O(3,2) or Sp(4), which is a subgroup of O(3,3) or SL(4,r), respectively. It is shown that among the six Sp(4)-like subgroups, only one possesses the symmetry which can be translated into the group of unitary transformations in quantum mechanics. (C) 1995 American Institute of Physics

BACKGROUND. Although computed tomography and magnetic resonance imaging have improved the staging and evaluation of non-small cell lung cancer (NSCLC), mediastinal staging lacks adequate specificity and sensitivity. Radioimmunodetection may augment computed tomography and magnetic resonance imaging. The authors evaluated the ability of the technetium 99m-anticarcinoembryonic antigen IMMU-4 Fab' fragment to localize NSCLC in vivo, measured its pharmacokinetics, and estimated its radiation dose. METHODS. Seventeen patients with carcinoembryonic antigen-positive NSCLC received 16-30 mCi of technetium 99m IMMU-4 Fab'. Planar imaging was performed at 1-7 hours and 20-24 hours. Single-photon emission computed tomography (SPECT) was performed within 8 hours after injection. In 10 patients, blood sampling, urine collection, and quantitative imaging were performed to determine blood and urine pharmacokinetics and radiation dose estimates. Human anti-mouse antibody response was measured for as long as 3 months after administration. RESULTS. Planar and/or SPECT imaging detected 72% of 32 known lesions. SPECT was more sensitive than planar imaging. T1/2 alpha averaged 0.18 +/- 0.33 hours; T1/2 beta averaged 8.02 +/- 5.53 hours. The mean concentration versus time value was 1.11 +/- 0.56 mg.h. The average whole body dose estimated for administration of 30 mCi was 0.45 +/- 0.08 rads. No human anti-mouse antibody responses were detected. CONCLUSION. The tumor detection rate was high, but the persistent blood pool at < 8 hours complicated image interpretation. An intermediate imaging time point (12-16 hours) might be preferable. SPECT is an important adjunct to imaging with this radioimmunoconjugate. The acceptable dosimetry estimated for 30 mCi Technetium 99m IMMU-4 Fab' and the lack of human anti-mouse antibody responses suggest this is a promising localizing tool for NSCLC

This study was undertaken to evaluate several concerns regarding the extradural space resulting from elective fronto-orbital advancement or frontal sinus cranialization techniques. The questions are (1) Do infants undergoing these techniques have the potential to obliterate this space at an accelerated rate, e.g., within 1 or 2 days? (2) Do adults have any potential to obliterate the space? (3) Do children obliterate the space like infants or like adults? (4) What is the specific time sequence for dead-space obliteration? Twenty patients ranging in age from 6 months to 35 years were studied before and after fronto-orbital advancement. The patients were divided into three groups: (1) infants (up to 15 months), (2) children (up to 9 years), and (3) adults (9 years and beyond). Postoperative intracranial dead space was assessed by serial CT scans. Ten patients had CT scans more than 14 days after surgery. These data demonstrate that intracranial dead space in infants is obliterated in a delayed fashion. Children tend to obliterate intracranial dead space in a manner similar to that of infants. Adults are able to obliterate the space over a longer, but finite, period of time as compared with infants and children. Part of the mechanism responsible for obliteration of the postoperative space may be enlargement of the ventricular system

Pharmacokinetics of radiolabeled BrE3 monoclonal antibody (Mab), reactive against a breast mucin epitope, were assessed in 15 patients with advanced breast cancer. Patients received 5 mCi (185 MBq) of 111In-methyl benzyl isothiocyanate DTPA (MX-DTPA) conjugated BrE-3 Mab intravenously with total antibody doses of 10, 50 or 100 mg. Serial quantitative imaging, blood and urine clearance were obtained to measure pharmacokinetics, assess tumor localization and estimate radiation dose. Organ function was followed to determine toxicity. Mild allergic reactions occurred in four patients. Eighty-six percent of 70 known lesions and 5 unsuspected lesions were detected by antibody imaging. Biexponential modeling of radiolabeled antibody in serum showed a T1/2 alpha = 9.5 +/- 2.7 hr and T1/2 beta = 56 +/- 25.4 hr. Total urinary excretion averaged 35.5% +/- 19.3% injected dose (ID) by Day 8. Quantitative imaging showed that 0.02-2.56% ID localized in tumors. Extrapolating dosimetry from 111In-MX-DTPA-BrE-3 to 90Y-MX-DTPA-BrE-3, we estimate therapeutic radiation doses could be delivered to some tumors with tolerable toxicity

Fifty-eight patients suspected of having focal hepatic disease were studied prior to and following the intravenous administration of manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (DPDP), a hepatobiliary magnetic resonance (MR) contrast agent. Four doses (3, 5, 8, or 10 mumol/kg) of Mn-DPDP were used to test the hypothesis that Mn-DPDP-enhanced MR imaging would display enhancement in tumors of hepatocellular origin. A total of 203 lesions were evaluated. Histologic proof was available in 32 cases, and in 26 cases lesions were evaluated on the basis of characteristic imaging findings. Statistical calculations for distinction of tumors of hepatocellular origin yielded a sensitivity of 100%, a specificity of 92.0%, an accuracy of 93.6%, a positive predictive value of 75.9%, and a negative predictive value of 100%. The authors conclude that the presence and patterns of enhancement at Mn-DPDP-enhanced MR imaging permit reliable distinction between hepatocellular and nonhepatocellular tumors

We evaluated the effect of the image acquisition parameters on the accuracy of the principal axes and surface-fitting techniques for three-dimensional image registration. Using two types of phantom objects, MR brain image and a mathematically defined ellipsoid, we simulated pairs of scans with known acquisition parameters, including longitudinal coverage, magnitude of mis-registration, number of sections and section thickness. Both methods are sensitive to the systematic deformation of contours. The principal axes method is also sensitive to incomplete scan coverage and to the x-axis and y-axis misangulation. Both methods are insensitive to the number of sections, section thickness and the number of points per section. Surface fitting performed well without user supervision. There is no need for routine inclusion of the scaling factors as search parameters. The results confirm the feasibility of three-dimensional multimodality registration of brain scans with accuracy 1-2 mm, with surface fitting being the method of choice

An integrated approach to existing methods of extracting biodistribution data, pharmacokinetics and radiation absorbed dose estimates from serial scintigraphic images is described. This approach employs a single computer-generated user interface to reformat planar scans into a standard file type, align conjugate (anterior and posterior) images, draw regions of interest (ROIs) over selected organs and lesions and generate count data for anterior and posterior views and calculated geometric means. Using standard correction methods, the fraction injected activity is obtained for all ROIs and total body. This methodology has been applied to the analysis of indium-III-labelled breast-cancer-directed antibodies and technetium-90m-labelled CEA-specific antibody fragments in non-small-cell lung cancer. It is anticipated that this approach will be useful for evaluating the dosimetry of other radiolabelled monoclonal antibodies, as well as other radiopharmaceuticals

PURPOSE: To test the hypothesis that atrophy of the hippocampal formation in nondemented elderly individuals would predict subsequent Alzheimer disease. METHOD: We studied 86 subjects at two time points, 4 years apart. At baseline all study subjects were nondemented and included 54 control subjects and 32 persons who had memory complaints and minimal cognitive impairments. All subjects received a CT scan using a protocol designed to image the perihippocampal cerebrospinal fluid (HCSF) accumulating in the fissures along the axis of the hippocampal formation. Blind to the clinical evaluations, we subjectively assessed the presence of HCSF at the baseline. Retrospectively, we examined the predicted association between baseline HCSF and clinical decline as determined across the two evaluations. RESULTS: At follow-up 25 of the 86 subjects had deteriorated and received the diagnosis of Alzheimer disease. Of the declining subjects, 23 came from the minimally impaired group, and 2 came from the control group. In the minimally impaired group the baseline HCSF measure had a sensitivity of 91% and a specificity of 89% as a predictor of decline. Both control subjects who deteriorated were also correctly identified at baseline. One of these two subjects died, and an autopsy confirmed the presence of Alzheimer disease. M(r) validation studies demonstrated that HCSF is quantitatively related to dilatation of the transverse fissure of Bichat and the choroidal and hippocampal fissures. CONCLUSION: Our findings strongly suggest that among persons with mild memory impairments, dilatation of the perihippocampal fissures is a useful radiologic marker for identifying the early features of Alzheimer disease

We have developed a graphical interface which allows users of varying levels of computer experience and proficiency to manipulate medical image-processing data with 'point-and-click' ease. The power which had formerly been associated with protocols and shell scripts has been combined with the flexibility and 'user-friendliness' of buttons and dialog boxes