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J L Humm

Publications and source records attributed to J L Humm.

At least 37 records · Page 2Linked to original sources
PubMed1999

131I radioimmunotherapy and fractionated external beam radiotherapy: comparative effectiveness in a human tumor xenograft.

UNLABELLED: This article compares the effectiveness of radiation delivered by a radiolabeled monoclonal antibody, 131I-labeled A33, that targets colorectal carcinoma, with that of 10 fractions of conventional 320 kVp x-rays. METHODS: Human colorectal cancer xenografts (SW1222) ranging between 0.14 and 0.84 g were grown in nude mice. These were treated either with escalating activities (3.7-18.5 MBq) of 131I-labeled A33 or 10 fractions of 320 kVp x-rays (fraction sizes from 1.5 to 5 Gy). Tumor dosimetry was determined from a similar group of tumor-bearing animals by serial kill, tumor resection and counting of radioactivity in a gamma counter. The relative effectiveness of the two radiation therapy treatment approaches was compared in terms of tumor regrowth delay and probability of tumor cure. RESULTS: The absorbed dose to tumor per MBq administered was estimated as 3.7 Gy (+/-1 Gy; 95% confidence interval). We observed a close to linear increase in tumor regrowth delay with escalating administered activity. Equitumor response of 1311 monoclonal antibody A33 was observed at average radiation doses to the tumor three times greater than when delivered by fractionated external beam radiotherapy. The relationship between the likelihood of tumor cure and administered activity was less predictable than that for regrowth delay. CONCLUSION: The relative effectiveness per unit dose of radiation therapy delivered by 131I-labeled A33 monoclonal antibodies was approximately one third of that produced by fractionated external beam radiotherapy, when measured by tumor regrowth delay.

Animals↗
PubMed1999

Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia.

UNLABELLED: Data from nine patients with leukemia participating in a phase I activity-escalation study of HuM195, labeled with the alpha-particle emitter 213Bi (half-life = 45.6 min), were used to estimate pharmacokinetics and dosimetry. This is the first trial using an alpha-particle emitter in humans. The linear energy transfer of alpha particles is several hundredfold greater than that of beta emissions. The range in tissue is approximately 60-90 microm. METHODS: The activity administered to patients ranged from 0.6 to 1.6 GBq. Patient imaging was initiated at the start of each injection. Thirty 1-min images followed by ten 3-min images were collected in dynamic mode; a 20% photopeak window centered at 440 keV was used. Blood samples were collected until 3 h postinjection and counted in a gamma counter. Contours around the liver and spleen were drawn on the anterior and posterior views and around a portion of the spine on the posterior views. No other organs were visualized. RESULTS: The percentage injected dose in the liver and spleen volumes increased rapidly over the first 10-15 min to a constant value for the remaining hour of imaging, yielding a very rapid uptake followed by a plateau in the antibody uptake curves. The kinetic curves were integrated to yield cumulated activity. The mean energy emitted per nuclear transition for 213Bi and its daughters, adjusted by a relative biologic effectiveness of 5 for alpha emissions, was multiplied by the cumulated activity to yield the absorbed dose equivalent. Photon dose to the total body was determined by calculating a photon-absorbed fraction. The absorbed dose equivalent to liver and spleen volumes ranged from 2.4 to 11.2 and 2.9 to 21.9 Sv, respectively. Marrow (or leukemia) mean dose ranged from 6.6 to 12.2 Sv. The total-body dose (photons only) ranged from 2.2 x 10(-4) to 5.8 x 10(-4) Gy. CONCLUSION: This study shows that patient imaging of 213Bi, an alpha-particle emitter, labeled to HuM195 is possible and may be used to derive pharmacokinetics and dosimetry. The absorbed dose ratio between marrow, liver and spleen volumes and the whole body for 213Bi-HuM195 is 1000-fold greater than that commonly observed with beta-emitting radionuclides used for radioimmunotherapy.

Acute Disease↗
PubMed1999

Thyroid cancer dosimetry using clearance fitting.

UNLABELLED: Since 1962, Memorial Sloan Kettering Cancer Center has used an individually optimized dosimetry method for patients with thyroid carcinoma undergoing radioiodine therapy. This traditional dosimetry method involves a determination of the maximum tolerated activity or the activity that will deliver 2 Gy to the blood (A(max)), and the corresponding ablative lesion dose (D(lesion)). However, the traditional calculations of A(max) and D(lesion) were based on empirical assumptions. The objective of this work was to develop a dosimetry method that eliminates these assumptions by incorporating patient kinetics and that is not restricted to 131I as a tracer and therapeutic agent. METHODS: Patient kinetics were incorporated into the dosimetry algorithm by fitting parameters to patient clearance measurements. The radioiodines 123I, 124I, 125I and 131I were accommodated as tracers and therapeutic agents by incorporating their physical half lives and by precalculating photon-absorbed fractions for these radionuclides for several thousand patient geometries using Monte Carlo simulations. RESULTS: A(max) and D(lesion) have been calculated using the traditional and new method for a group of patients, and errors associated with each of the above assumptions were examined. Assuming that the initial blood activity is distributed instantaneously in 5 L was found to introduce an error in A(max) of up to 30%, whereas assuming physical decay beyond the last data point introduced an error of up to 50%. CONCLUSION: Individualized fitting of clearance data is a practical method to accurately account for inter-patient kinetics variations. The substitution of standard kinetics beyond measured data might lead to substantial errors in estimating A(max) and D(lesion). In addition, gamma camera images, rather than neck probe readings, should be used to determine lesion uptakes for thyroid cancer patients.

Humans↗
PubMed1998

Use-dependent exacerbation of brain damage occurs during an early post-lesion vulnerable period.

For a period of time after unilateral brain injury, surviving neural tissue surrounding the lesion may be vulnerable to extremely high behavioral demand. Previously, we found that lesions of the forelimb representation area of the sensorimotor cortex (FL-SMC) in rats increase in size substantially when the intact forelimb is immobilized with a plaster of paris cast during the first 15 days after surgery, which forces overuse of the impaired forelimb. The present study was designed to determine whether the adult brain is more vulnerable to forced overuse of the impaired forelimb during the first 7 days post-lesion than during the second 7 days post-lesion. Using behavioral tests of forelimb use and stereological analysis of remaining tissue volume 40 days after FL-SMC lesions, we found that forced overuse of the impaired forelimb during the first 7 days after the initial damage caused expansion of neural injury and greatly interfered with restoration of function. In contrast, forced overuse of the impaired forelimb during the second 7 days had no significant effect on lesion size but nevertheless interfered with restoration of function. Thus, surviving neural tissue in the damaged hemisphere and recovery of function appear to be vulnerable to prolonged forced overuse of the impaired forelimb throughout the first 15 days, but tissue loss was detectable only when the animal was forced to use the impaired forelimb during the first 7 days after injury.

Animals↗
PubMed1998

Electron wedges for radiation therapy.

PURPOSE: Brain tumors can be advantageously treated with electron over photon radiation, by exploiting the rapid fall-off in dose with depth. This advantage could be further enhanced by utilizing multiple electron beams. However, in some beam configurations, wedged dose profiles would be necessary for the dose uniformity. Unlike photons, shaped pieces of material placed in electron beam severely degrade the energy, give additional scattering and, therefore, are suboptimal. The purpose of this study was to create wedged electron fields, using intensity modulation. The combination of electron wedges enables a more uniform coverage of brain tumors with a reduced dose to normal tissue. METHODS AND MATERIALS: Intensity modulation was performed for 10 to 50 MeV electrons using a narrow scanning elementary beam of a racetrack Microtron accelerator, delivering radiation pulses with coordinates and intensities prescribed by a custom scan matrix. Dispensing more pulses (or longer pulses) within the field to increase the local dose, one can sharpen the penumbra at depth and generate wedged dose distributions of arbitrary angle as well as many other desired profiles. We modulated the electron beams, measured dose distributions using film in an anthropomorphic phantom, and compared the results with conventional techniques. RESULTS: Intensity modulation of electron beams decreases the 50-90% penumbra at depth by 40% and increases the flatness by 80%. Wedged profiles at depth can be created for any angle up to about 70 degrees, depending on the beam energy. Multiple modulated electron beams give smaller 20-70% but larger 70-100% isodose regions than photon beams. CONCLUSIONS: Electron beams can improve dose distributions in brain compared to the same number of photon beams, reducing the 20-70% isodoses region in normal tissue by 30%. Intensity modulation significantly improves the dose distribution from combined electron beams providing a sharper penumbra, better conformity, and reduced margin.

Brain Neoplasms↗
PubMed1998

Radioimmunotherapy with alpha-emitting nuclides.

This review discusses the application of alpha particle-emitting radionuclides in targeted radioimmunotherapy. It will outline the production and chemistry of astatine-211, bismuth-212, lead-212, actinium-225, bismuth-213, fermium-255, radium-223 and terbium-149, which at present are the most promising alpha-emitting isotopes available for human clinical use. The selective cytotoxicity offered by alpha particle-emitting radioimmunoconstructs is due to the high linear energy transfer and short particle path length of these radionuclides. Based upon the pharmacokinetics of alpha particle-emitting radioimmunoconstructs, both stochastic and conventional dosimetric methodology is discussed, as is the preclinical and initial clinical use of these radionuclides conjugated to monoclonal antibodies for the treatment of human neoplasia.

Alpha Particles↗
PubMed1998

Pharmacokinetic model of iodine-131-G250 antibody in renal cell carcinoma patients.

UNLABELLED: A model that describes the pharmacokinetic distribution of 131I-labeled G250 antibody is developed. METHODS: Previously collected pharmacokinetic data from a Phase I-II study of 131I-G250 murine antibody against renal cell carcinoma were used to develop a mathematical model describing antibody clearance from serum and the whole body. Survey meter measurements, obtained while the patient was under radiation precautions, and imaging data, obtained at later times, were combined to evaluate whole-body clearance kinetics over an extended period. RESULTS: A linear two-compartment model was found to provide good fits to the data. The antibody was injected into Compartment 1, the initial distribution volume (Vd) of the antibody, which included serum. The antibody exchanged with the rest of the body, Compartment 2, and was eventually excreted. Data from 13 of the 16 patients fit the model with unique parameters; the maximum, median and minimum values for model-derived Vd were 6.3, 3.7 and 2.11, respectively. The maximum, median and minimum values for the excretion rate were 8 x 10(-2), 2.4 x 10(-2) and 1.3 x 10(-2) hr(-1), respectively. Parameter sensitivity analysis showed that a change in the transfer rate constant from serum to the rest of the body had the greatest effect on serum cumulative activity and that the rate constant for excretion had the greatest effect on whole-body cumulative activity. CONCLUSION: A linear two-compartment model was adequate in describing the serum and whole-body kinetics of G250 antibody distribution. The median initial distribution volume predicted by the model was consistent with the nominal value of 3.81. A wide variability in fitted parameters was observed among patients, reflecting the differences in individual patient clearance and exchange kinetics of G250 antibody. By selecting median parameter values, such a model may be used to evaluate and design prolonged multiple administration radioimmunotherapy protocols.

Adult↗
PubMed1997

Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding.

BACKGROUND: It is common protocol in radionuclide therapies to administer a tracer dose of a radiopharmaceutical, determine its lesion uptake and biodistribution by gamma imaging, and then use this information to determine the most effective therapeutic dose. This treatment planning approach can be used to quantitate accurately the activity and volume of lesions and organs with positron emission tomography (PET). In this article, the authors focus on the specification of appropriate volumes of interest (VoI) using PET in association with computed tomography (CT). METHODS: The authors have developed an automatic image segmentation schema to determine the VoI of metastases to the lung from PET images, under conditions of variable background activity. An elliptical Jaszczak phantom containing a set of spheres with volumes ranging from 0.4 to 5.5 mL was filled with F-18 activity (2-3 microCi/mL) corresponding to activities clinically observed in lung lesions. Images were acquired with a cold background and then with variable source-to-background (S/B) ratios of: 7.4, 5.5, 3.1, and 2.8. Lesion VoI analysis was performed on 10 patients with 17 primary or metastatic lung lesions, applying the optimum threshold values derived from the phantom experiments. Initial volume estimates for lung lesions were determined from CT images. Approximate S/B ratios were obtained for the corresponding lesions on F-18-fluoro-2-deoxy-D-glucose (18FDG)-PET images. From the CT estimate of the lesion size and the PET estimate of the S/B ratio, the appropriate optimum threshold could be chosen. The threshold was applied to the PET images to obtain lesion activity and a final estimate of the lesion volume. RESULTS: Phantom data analysis showed that image segmentation converged to a fixed threshold value (from 36% to 44%) for sphere volumes larger than 4 mL, with the exact value depending on the S/B ratios. For patients, the use of optimum threshold schema demonstrated a good correlation (r = 0.999) between the initial volume from CT and the final volume derived from the 18FDG-PET scan (P < 0.02). The mean difference for those volumes was 8.4%. CONCLUSIONS: The adaptive thresholding method applied to PET scans enables the definition of tumor VoI, which hopefully leads to accurate tumor dosimetry. This method can also be applied to small lesions (<4 mL). It should enable physicians to track objectively changes in disease status that could otherwise be obscured by the uncertainties in the region-of-interest drawing, even when the scans are delineated by the same physician.

Aged↗
PubMed1997

Preoptic area infusions of morphine disrupt--and naloxone restores--parental-like behavior in juvenile rats.

As in the adult lactating female, opioids disrupt (and naloxone restores), parental behavior in juvenile rats (approximately 25 days of age). Because the preoptic area regulates the display of parental behavior in lactating females, we examined its parental behavior role in the juvenile rat. At 21 days of age, juvenile rats were implanted with bilateral cannulae aimed at the preoptic area using a modified Kopf stereotaxic and extrapolating from a developing-rat brain atlas [58], and divided into two groups: Initiation and maintenance. On day 25, the initiation group received bilateral infusions of either morphine (0.50 microgram), saline (0.25 microliter), or morphine plus naloxone (0.25 microgram). Thirty minutes later, they were exposed to three 1-6-day-old pups; the maintenance group was exposed to pups until they displayed 2 consecutive days of parental behavior, then infused. Morphine disrupted parental behavior in both the initiation and Maintenance groups, and naloxone restored the behavior to control/ saline levels. Parental behavior in the juvenile animal of both sexes, therefore, is under opioid regulation that parallels the adult female.

Animals↗
PubMed1997

Use-dependent structural events in recovery of function.

We described research suggesting that forelimb use is essential for marked neural growth in the intact cortex after unilateral forelimb-cortical lesions. Although unilateral brain injury can cause severe functional impairment, the injury may be capable of mobilizing potent resources for compensatory changes such as dendritic arborization in the noninjured hemisphere, but only for a limited period of time and only with appropriate behavioral pressure. Unexpectedly, surviving tissue in the injured hemisphere may be fatally vulnerable to excessive behavioral demand. If the impaired limb is overused because the nonimpaired limb is restricted by a one-sleeve cast, injury size is greatly increased and recovery of function is severely disrupted. It is hypothesized that behaviorally driven neurotransmitter release relating to forced use of the forelimb may be toxic to surviving tissue that has been partially traumatized by the lesion. These data and hypotheses are summarized in Fig. 7. The "use-it-or-lose-it" rehabilitative approach is popular, but perhaps a less aggressive strategy should be adopted for optimal restoration of function in the injured hemisphere. Whereas traditional experiments on mechanisms of recovery of function are designed specifically to determine potentially compensatory neural changes that might mediate behavioral outcome, these experiments support a quite different view of the interplay between neural and behavioral events: behavioral changes may directly alter anatomical events.

Animals↗
PubMed1997

Quantitative bone metastases analysis based on image segmentation.

UNLABELLED: Preliminary evidence indicates that the fraction of bone containing metastatic lesions is a strong prognostic indicator of survival longevity for prostate and breast cancer. Our current approach to quantify metastatic bone lesions, called the Bone Scan Index, is based on an inspection of the bone scan, estimating visually the fraction of each bone involved and then summing across all bones to determine the percentage of total skeletal involvement. This approach, however, is time consuming, subjective and dependent on individual interpretation. METHODS: To overcome these problems, a semiautomated image segmentation program was developed for the quantitation of metastases from planar whole-body bone scans. The user is required to insert a seed point into each metastatic region on the image. The algorithm then connects pixels to the seed pixel in all directions until a contrast-dependent threshold is reached. The optimal threshold for cessation of the region growing is determined from phantom studies. On the images, lesion delineation and size measurements were performed by the algorithm. Each delineated lesion is associated with a bone site using pull-down menus. The program then computes the fraction of lesion involvement in each bone based on look-up-tables containing the relationship of bone mass with race, sex, height and age. These look-up-tables were obtained by multiple regression of the skeletal mass measurements in humans. The total fraction of skeletal involvement is then obtained from the individual fractional masses. For individual fractional mass, values given in International Commission on Radiation Protection Publication No. 23 were used. RESULTS: The bone metastases analysis system has been used on 11 scans from 6 patients. The correlation was high (r = 0.83) between conventional (manually drawn region-of-interest) and this analysis system. Bone metastases analysis results in consistently lower estimates of fractional involvement in bone compared with the conventional region-of-interest drawing or visual estimation method. This is due to the apparent broadening of objects at and below the limits of resolution of the gamma camera. CONCLUSION: Image segmentation reduces the delineation and quantitation time of lesions by at least two compared with manual region-of-interest drawing. The objectivity of this technique allows the detection of small variations in follow-up patient scans for which the manual region-of-interest method may fail, due to performance variability of the user. This method preserves the diagnostic skills of the nuclear medicine physician to select which bony structures contain lesions, yet combines it with an objective delineation of the lesion.

Adolescent↗
PubMed1997

Distribution of radiolabeled monoclonal antibody MX35 F(ab')2 in tissue samples by storage phosphor screen image analysis: evaluation of antibody localization to micrometastatic disease in epithelial ovarian cancer.

Our objective was to quantify the targeting of the monoclonal antibody (mAb) MX35 F(ab')2 to micrometastatic epithelial ovarian cancer. This mAb detects a Mr 95,000 glycoprotein with homogeneous distribution on 80% of ovarian tumor specimens. Six patients with minimal residual disease from an imaging trial were injected with 2 or 10 mg of 131I- and 125I-labeled mAb MX35 F(ab')2. Biopsied samples were removed at second-look laparotomy 1-5 days post-i.v. or -i.p. infusion of antibody. Serial cryostat sections were stained by indirect immunoperoxidase method for antigen distribution and exposed to storage phosphor screens for quantitative autoradiography. Coregistration of tumor histology, antigen expression, and radionuclide distribution demonstrated specific localization in micrometastatic tumor foci (50 micrometer to 1 mm) found within tissue stroma. The radiolabeled antibody uptake determined by well scintillation counts ranged between 5.2 and 223.5 x 10(-4) percentage of injected dose/g of tumor tissue for 131I. Specific localization of mAb in tumor was determined by tumor:normal tissue (fat) ratios ranging from 0.9:1 to 35.9:1 for 131I. The high resolution and linear response of the storage phosphor screen imager was used to estimate the radionuclide activity localized in each micrometastatic site. Quantitation of phosphor screen response revealed microCi/g values of 0.026-0.341 for normal tissue and 0.184-6.092 for tumor biopsies, evaluated 4 or 5 days post-antibody injection. The tumor:normal tissue (adjacent to tumor) ratios were between 1 and 4 times greater using the phosphor screen method than well counter measurements, but even larger variations of ratios up to 20:1 were observed between tumor cell foci and stromal cells within the same tissue section. This study has demonstrated that mAb MX35 F(ab')2 localizes to the micrometastatic ovarian carcinoma deposits within the peritoneal cavity. The dosimetry results suggest a therapeutic potential for this antibody in patients with minimal residual disease (<5 mm).

Antibodies, Monoclonal↗
PubMed1996

Dosimetric properties of a scanned beam microtron at low monitor unit settings: importance for conformal therapy.

The dosimetric stability, linearity, dose rate dependence, and flatness of both photon and electron beams have been evaluated for a racetrack microtron at low monitor unit settings. For photons, the variation in dosimetric output about the mean is < 0.4% at 100 monitor units (MU), < 1% at 10 MU, and < 4% at 2 MU. The output dependence on the dose rate varied by < 0.6% between 85-300 MU/min. Flatness and symmetry for the 25- and 50-MV beams showed deviations of < 3% at both dmax and 10-cm depths, and only slightly > 3% at 20 cm, even at only 3 MU, in contrast with other scanned beam accelerators. Broad electron beams on the microtron are created by the superposition of the elementary beam pulses either directly from the scan magnets, or after their broadening through a scattering foil. The dosimetric instability both with and without the foil was less than 0.6% for both the 25- and 50-MeV electrons. Dose nonlinearity was < 1% above 10 MU. Field flatness was determined for scan matrices designed to produce a flat field both with and without a scattering foil. Symmetry and flatness deviations were < 3% for both electron energies when a scattering foil was used, even for a single scan. The variation of the electron dose per monitor unit between dose rates of 85-300 MU/min was < 1% (25 MeV) and < 4% (50 MeV) when a scattering foil was used, but as high as 22% (25 MeV) and 36% (50 MeV) for broad beams generated by elementary beam pulses directly from the scanning magnets. The microtron exhibits dosimetric properties which fulfill the recommendations of Task Groups 21 and 25. Based on the stability of the scanned beam at low monitor unit settings, the microtron can be used for 3-D conformal therapy with both photons and electrons.

Biophysical Phenomena↗
PubMed1996

Electron dose profile shaping by modulation of a scanning elementary beam.

The use of multiple high energy electron beams has been limited in the treatment of deep seated tumors. This is principally because of the rapid increase in the physical electron beam penumbra as a result of the rise in large angle scattering with depth in the patient. This decreases the transverse dose gradient between the target volume and sensitive dose limiting structures and diminishes the ability to conform electron isodose lines to the target volume. If the beam is flat in air, then its profile will become progressively more rounded with depth, due to the increase of scatter out of the beam edges. With a scanning elementary electron beam, such as produced by the Microtron MM50, the characteristics of a broad beam profile are determined by the scan pattern. Using an appropriate scan pattern one can create, at any depth within the range of electrons, various dose profiles with the sharpness not exceeding that of the elementary beam. The objective of this work was to study methods that produce the desired electron beam profile at the depth of the target volume, and to derive the surface fluence profile required. Two approaches were explored to modulate the elementary beam distribution: "amplitude modulation" (AM) and "frequency modulation" (FM). We calculated coordinate and intensity distributions of the 25, 40, and 50 MeV elementary beam pulses at the surface that would yield a flat field at various prescribed depths. The results are in good qualitative agreement with iterative deconvolution calculations by Brahme et al. [Acta Radiol. Oncol. 19, 305-319 (1980)]. The scattering penumbra between the 50%-90% isodose lines can be reduced by up to 40% by beam modulation. The modulation should also enable the combination of multiple electron beams so as to achieve the desired conformal isodose profile as is customarily seen with photon beam planning, but with greater normal tissue sparing due to higher electron longitudinal depth--dose gradients. The results can be also used for electron accelerators that do not use a scanning elementary beam.

Algorithms↗
PubMed1996

Pharmacokinetics and dosimetry of iodine-125-IUdR in the treatment of colorectal cancer metastatic to liver.

UNLABELLED: The radiotoxicity of 125I is highly sensitive to the site of decay relative to nuclear DNA. This paper describes a new approach, based upon pharmacokinetic clearance of radioactivity from the tumor, with which to quantify the fraction of [125I]IUdR incorporated within the DNA of tumor cells. METHODS: Patients were injected with [125I]IUdR through the hepatic artery. Iodine-131-IUdR was used as a tracer for imaging and quantitation. Both conventional and DNA-level dosimetry were performed. RESULTS: We calculated that if 15% of the tumor cells were in S phase at the time of injection, there would be 250 decays of 125I in the DNA per tumor cell after an infusion of 5 mCi [125I]IUdR. According to in vitro data based on 5 x 10(8) cells per g tumor, 99% of these cells in S phase would be killed. CONCLUSION: The estimate of cell inactivation is strongly dependent on the number of cells per gram and the fraction of cells in S phase at the time of injection, which indicates that repeat injections would be necessary to achieve a therapeutic effect.

Bone Marrow↗
PubMed1995

Collision detection and avoidance during treatment planning.

PURPOSE: To develop computer software that assists the planner avoid potential gantry collisions with the patient or patient support assembly during the treatment planning process. METHODS AND MATERIALS: The approach uses a simulation of the therapy room with a scale model of the treatment machine. Because the dimensions of the machine and patient are known, one can calculate a priori whether any desired therapy field is possible or will result in a collision. To assist the planner, we have developed a graphical interface enabling the accurate visualization of each treatment field configuration within a "room's eye view" treatment planning window. This enables the planner to be aware of, and alleviate any potential collision hazards. To circumvent blind spots in the graphic representation, an analytical software module precomputes whether each update of the gantry or turntable position is safe. RESULTS: If a collision is detected, the module alerts the planner and suggests collision evasive actions such as either an extended distance treatment or the gantry angle of closest approach. CONCLUSIONS: The model enables the planner to experiment with unconventional noncoplanar treatment fields, and immediately test their feasibility.

Computer-Aided Design↗
PubMed1995

Paucity of c-fos expression in the medial preoptic area of prenatally stressed male rats following exposure to sexually receptive females.

Normal male rats display high levels of sexual activity when paired with sexually receptive females, a behavior regulated, in large part, by the medial preoptic area (MPOA). It has been documented that onset of c-fos proteins in the MPOA accompanies sexual behavior. Because prenatal stress (PS) demasculinizes sexual behavior in male rats, the present study examined whether such effects might be accompanied by a decrease in the neuronal activation in MPOA associated with sexual behavior. Adult prenatally stressed (P-S) and unstressed control males were paired with sexually receptive females, and sexual behavior allowed to commence. After a single mount, the pair was separated by a partition for the remainder of an hour, at the end of which the male was killed and the brain processed for c-fos immunocytochemistry; quantification was performed by means of computerized image analysis. P-S males expressed significantly less c-fos activity in the region of the MPOA, compared to nonstressed control males. Thus, the sexual deficits associated with P-S males may be due to a relative dearth of activity in the MPOA at the neuronal level. Coupled to earlier work showing decreased luteinizing hormone secretion in P-S males under similar conditions, the present data suggest a constellation of factors that contribute to PS-induced deficits in sexual behavior.

Animals↗