Biomedical subjects
J Beatty
Publications and source records attributed to J Beatty.
Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases.
PURPOSE: A feasibility study addressing the role of a new miniature x-ray device, the Photon Radiosurgery System (PRS), for interstitial radiosurgical treatment of intracranial metastatic neoplasms, was conducted at our institution. To gain insight into the role of PRS vis-à-vis other currently available radiosurgical treatment modalities, dosimetric comparisons of Linac Radiosurgery and proton beam therapy were performed in the treatment of a small approximately spherical metastasis. METHODS AND MATERIALS: The photon radiosurgery system is a miniature, battery operated, high-voltage x-ray generator that produces low-energy x-rays with an effective energy of 10-20 keV emanating from the tip of a probe stereotactically inserted into small tumors (< 3 cm in diameter) in humans. Patients, 18 years or older, with supratentorial mass lesions less than 3 cm in diameter were eligible if they were likely to survive their systemic cancer and be capable of self-care for more than 4 months. Patients were ineligible if presenting with infratentorial lesions, contraindications for biopsy, or receipt of chemotherapy or radiotherapy within 4 weeks were ineligible. RESULTS: Fourteen patients with metastatic supratentorial lesions were treated from December 1992 to December 1993 for metastatic tumors to the brain. Single doses of 10-20 Gy were delivered to spherical targets of 10 to 35 mm in diameter. Treatment, including biopsy, pathologic review and radiation treatment, generally took less than 3 h. One patient, later found to have an ischemic stroke, developed a small hemorrhage from the biopsy that preceded interstitial irradiation. There were no other complications. Median survival was 10 months. Three locally recurrent lesions failed at 3.5, 4, and 10 months after treatment. All patients had stable or improved Karnofsky status for 2 weeks to 21 months after treatment. The PRS dosimetry appears at least as good as that obtained using 6 MV Linac or 160 MeV protons. Analyses of dose-volume histograms comparing the volumes of normal CNS tissue irradiated employing each of the respective modalities suggest a small sparing of normal tissue with PRS, as opposed to linac or protons, in this patient population with small, approximately spherical tumors. CONCLUSIONS: The PRS device provides a unique cost and time efficient procedure for providing interstitial radiation therapy immediately following histologic confirmation of malignancy in patients undergoing biopsy of intracranial lesions. The PRS treatment appears safe, and preliminary data suggest no evidence of treatment-related morbidity within the life span of the selected patient population. When treating small, spherical lesions, PRS appears to offer a modest dosimetric advantage over Linac or proton beam therapy in sparing normal tissue. These encouraging results have prompted a Phase II trial that is currently underway. Further efforts are necessary in the design of a clinically relevant trial addressing the role of fractionated external beam radiation therapy with boost vs. PRS treatment with WBRT in the treatment of single metastases.
A method for predicting the variation of the depth of maximum dose in shaped electron fields.
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A new miniature x-ray device for interstitial radiosurgery: dosimetry.
A miniature, battery operated 40 kV x-ray device has been developed for the interstitial treatment of small tumors ( < 3 cm diam) in humans. X rays are emitted from the tip of a 10 cm long, 3 mm diameter probe that is stereotactically inserted into the tumor. The beam, characterized by half-value layer (HVL), spectrum analysis, and isodose contours, behaves essentially as a point isotropic source with an effective energy of 20 keV at a depth of 10 mm in water. The absolute output from the device was measured using a parallel plate ionization chamber, modified with a platinum aperture. The dose rate in water determined from these chamber measurements was found to be nominally 150 cGy/min at a distance of 10 mm for a beam current of 40 microA and voltage of 40 kV. The dose in water falls off approximately as the third power of the distance. To date, 14 patients have been treated with this device in a phase I clinical trial.
Bone marrow transplantation for sickle cell anemia.
PURPOSE: To investigate the role of bone marrow transplantation in patients with severe sickle cell anemia (SCA). PATIENTS AND METHODS: We have designed a protocol for selecting patients with severe SCA who may benefit from bone marrow transplantation (BMT). On the basis of this protocol, a girl 3 9/12 years of age who had severe recurrent pain crises and splenic dysfunction received a BMT from her brother, who is homozygous for hemoglobin A. RESULTS: Transplantation resulted in prompt engraftment, followed by durable hematologic and immunologic reconstitution with donor cells. One year after BMT, the patient continued to do well. She did not experience any graft versus host disease, her growth velocity increased, and recovery of splenic function was demonstrated. Since undergoing BMT, she has not experienced any painful crises. CONCLUSIONS: Bone marrow transplantation is an effective therapeutic modality that should be considered in patients with severe SCA.
Magnetoencephalographic localization of a language processing cortical area adjacent to a cerebral arteriovenous malformation. Case report.
In order to accurately estimate the risk of surgery for dominant perisylvian arteriovenous malformations, the topographical relationship of the lesion to language cortex must be determined. A case is presented in which a magnetoencephalographic (MEG) study was used to map preoperatively and noninvasively an intracortical source of speech-receptive cortex in a 25-year-old right-handed man with a dominant left temporal lobe arteriovenous malformation. The speech-evoked magnetic field was analyzed at 36 positions over the left hemisphere in response to presentations of the consonant-vowel syllables "da" and "ga." A topographical map of the magnetic component evoked at 110 msec after stimulus onset, which was negative going to the vertex in concurrent electrical recordings, was congruent with a superficial cortical neuronal current source. This source was displaced from that usually observed in normal individuals to tonal or click stimuli, being superior to the probable location of auditory cortex, and superior and anterior to the probable location of Wernicke's area as conventionally described. The MEG results were in accord with the determination of position of a language-processing cortical area as assessed by direct electrical stimulation of the cortex during surgery under local anesthesia, and by superselective Amytal (amobarbital) injection during angiography. The MEG recordings and exposed brain stimulation sites were coordinated by cranial measurements, skull x-ray landmarks, and angiographic anatomy. Investigations such as this, which compare MEG findings with those from established clinical procedures, are an essential step in determining the physiological and anatomical utility of magnetoencephalography for noninvasive clinical functional localization.
Prolongation of magnetic resonance T2 time in hippocampus of human patients marks the presence and severity of Alzheimer's disease.
Spin-spin relaxation time (T2) was measured in the hippocampal formation, thalamus, and cortical white matter in 13 patients with probable Alzheimer's disease (AD), 11 elderly normal individuals, 23 healthy young persons, and 9 subjects diagnosed with multi-infarct dementia. A 0.04 tesla magnetic resonance scanner was used. Hippocampal T2 values for all AD patients exceeded those of any non-AD individual, regardless of age or dementia due to infarction. Further, these T2 values were highly correlated (+ 0.96) with the severity of functional and cognitive impairment of the AD patients. This T2 prolongation was not observed at the other sites examined. These results suggest that hippocampal T2 prolongation may provide a specific marker by which AD pathology can be detected, characterized, and followed in vivo.
Remotely controlled positioning lasers.
Positioning lasers used in radiotherapy generally require little adjustment. When required, this is easy to do for sidelights, but can be difficult and time consuming for ceiling mounted lasers. For this purpose, we have modified a commercial positioning laser by incorporating a device for rotating the alignment adjustment screws. This device is driven by a pair of motors remotely controlled through a cable. Two units have been built and installed. In practice, experience with these drive units has shown that it is now easier to adjust the ceiling lasers than the sidelights. Adjustment sensitivity in both units is considerably better than 1 mm, so there is little problem aligning the laser quickly and accurately.
Group A variants defined with a monoclonal anti-A reagent.
Unusual serologic findings mimicking the B(A) phenomenon were noted in two group B blood donors using blended murine monoclonal anti-A reagent. With additional studies, including a binding experiment using affinity chromatography, the presence of aberrant group A activities was confirmed. This observation suggests that persons with atypical B(A) phenotype may warrant further investigation to delineate the ABO blood group.
Ureteric ganglia in the guinea pig.
We studied the ureter of guinea pigs to ascertain whether there are ganglia and ganglion neurons directly associated with this structure. We consistently observed ureteric ganglia and individual neurons in the adventitia of the ureter or very close to it. There were on average 87 neurons per ureter, and they were scattered over the entire length of the tube.
Contrasting effects of response uncertainty on the task-evoked pupillary response and reaction time.
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Intracellular currents of interictal penicillin spikes: evidence from neuromagnetic mapping.
To analyze the net intracellular current produced by interictal spikes, we mapped the extracranial magnetic fields of the rat brain following application of penicillin to the right or left medial cingulate cortex. Averaged interictal spikes in both the magnetoencephalogram (MEG) and in the electrocorticogram (ECoG) were composed of 4 temporal components, a biphasic spike and slow wave. Magnetic field maps for each of these components indicated a source at the location of penicillin application, with intracellular currents oriented perpendicular to the surface of the cingulate cortex, along the axis of the major pyramidal cells. The polarity of the magnetic fields for each of the components was reversed between the two cingulate groups, reflecting the respective orientation of pyramidal cells between the juxtaposed faces of the medial cingulate cortex. This neuromagnetic study of net intracellular current complements and extends the analysis of extracellular currents within the penicillin focus obtained using laminar electrodes. These data also demonstrate how animal neuromagnetometry may provide an empirical foundation for the neurogenesis of the MEG and a new unique method for the non-invasive study of population cell physiology.
Magnetic localization of a dipolar current source implanted in a sphere and a human cranium.
Magnetic fields produced by a dipolar source implanted in a spherical conductor and a human cranial specimen were measured in the magnetoencephalogram (MEG). The location of the source was accurately computed in the spherical conductor from the identified magnetic field extrema using equations for a current dipole in a sphere. This same method was insufficient for localizing the source in a human cranium, where magnetic field maps appeared as distortions from the classical dipolar pattern. A more complete computer modeling procedure was used, adjusting for the non-spherical dimensions of the recording matrix on the cranium. By fitting the gradient of computer simulated fields to those measured outside the cranium, the accuracy of source localization was substantially improved. The greatest distortion of the extracranial magnetic field was an inequality in the measured amplitude of the two extrema, produced by an increased distance and angle of the MEG probe when recording over the lower face and ear. However, gross heterogeneities in the resistance of the skull due to a craniectomy and an implanted insulating balloon had a negligible effect on the extracranial magnetic field pattern.
Pupillary dilations in movement preparation and execution.
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The pupil and stimulus probability.
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Fast and slow magnetic phenomena in focal epileptic seizures.
The magnetic fields associated with penicillin-induced focal epilepsy were measured in laboratory rats. Interictal magnetic spikes were similar to those previously observed in humans with focal seizure disorders. The magnetic fields of the seizure itself displayed both slow and fast phenomena, reversing in direction on opposite sides of the head.
Neuromagnetic evidence of spatially distributed sources underlying epileptiform spikes in the human brain.
Neuromagnetic measurements were performed on 17 subjects with focal seizure disorders. In all of the subjects, the interictal spike in the scalp electroencephalogram was associated with an orderly extracranial magnetic field pattern. In eight of these subjects, multiple current sources underlay the magnetic spike complex. The multiple sources within a given subject displayed a fixed chronological sequence of discharge, demonstrating a high degree of spatial and temporal organization within the interictal focus.
Quantification of the utilization of reserve oxygen transport capacity: initial studies in critically ill patients.
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