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Magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques were used to obtain in vivo scans of delayed (30 GyE helium ion, 230 MeV/u) radiation injury in rabbit brain. T2-weighted (T2W) MRI scans demonstrated alterations that were restricted primarily to the white matter tracts and the deep perithalamic and thalamic regions. Quantitative measurements of T2 and T1 values demonstrated wide variations in absolute values. However, paired comparisons in hemibrain-irradiated rabbits revealed significant increases in T2 (p less than 0.001) and T1 (p less than 0.01) in irradiated versus unirradiated brain. Gadolinium DTPA (GdDTPA) enhanced MRI and 82Rubidium (82Rb) PET detected focal regions of blood-brain barrier (BBB) disruption restricted to the deep white matter and thalamic regions. Sequential GdDTPA enhanced MRI scans showed the spreading of the tracer from the initial site of contrast enhancement. 18Fluorodeoxyglucose (18FDG) PET studies demonstrated the markedly depressed metabolic profiles of irradiated brain. Histological findings of tissue edema and necrosis correlated well with the in vivo imaging abnormalities. These initial studies demonstrate that the irradiated rabbit brain is a suitable animal model for examining the delayed effects of radiation injury in the brain.

Stereotactic radiosurgery has proven to be an effective method of treating selected inaccessible or inoperable arteriovenous malformations (AVMs) of the brain. Radiation-induced obliteration of successfully-treated AVMs, however, occurs only after some latent period after treatment, depending on size, location, and dose. An experimental compartmental flow model is proposed to describe the hemodynamic alterations in the AVM as a result of the pathophysiological changes after radiosurgery, and to analyze temporal alterations in AVM blood flow rates and pressure gradients before complete obliteration. In representative small (low-flow, 150 ml/min) and large (high-flow, 440 ml/min) AVMs, it is found that increases in pressure gradients across certain vascular structures within the AVM occur during the normal course of radiation-induced flow decrease and AVM obliteration. The magnitude of these pressure alterations, however, may be within the normal physiological variations in cerebrovascular blood pressure. The effects of partial-volume irradiation of the AVM is examined by limiting radiosurgical treatment to varying portions of the flow compartments within the model. It is found that alterations in pressure gradients persist in unirradiated vascular shunts, even after complete obliteration of the treated AVM volume. These pressure alterations may increase the probability of hemorrhage from the untreated shunts of the AVM and cause redistribution of regional cerebral blood flow resulting in increased flow through these untreated shunts.

A new beam line for radiotherapy and radiosurgery with accelerated helium-ion beams has been set up at the Bevalac. The new treatment room has been equipped with a very precise patient positioner in order to utilize the superior dose localization properties of light-ion beams. The beam spreading and shaping system is described, the trade-offs involved in positioning the beam modifying devices are discussed, and the physical properties of the generated radiation fields are reported. The Bragg peak modulation by axial beam stacking employing a variable range shifter is explained and the control system including beam monitoring and dosimetry is presented.

Between July 1983 and July 1989, we treated 35 patients with surgically inaccessible, symptomatic angiographically occult vascular malformations (AOVMs) using stereotactic heavy-charged-particle radiosurgery. AOVMs were located in the brainstem (19), thalamus or internal capsule (9), basal ganglia (3), deep cerebral hemisphere and motor area (3), or cerebellopontine angle (1). All patients presented with clinical and radiological evidence of previous hemorrhage, usually with multiple episodes of hemorrhage. Treatment volumes ranged from 80 to 15,200 mm3 and treatment doses from 7.7 to 34.6 Gy. Mean follow-up was 40 months, with 31 patients followed for at least 2 years. Clinical outcome was excellent in 46%, good in 34% and poor in 14%; 6% died. Twenty-seven patients in excellent and good condition prior to treatment remained stable or improved neurologically. Two patients initially in poor condition, who had previously received conventional radiotherapy, died at 9 and 14 months after treatment, respectively. Six patients experienced recurrent hemorrhage 2-60 months following treatment. Three of these patients made a complete recovery. Although a larger number of treated patients must be followed over longer periods of time, stereotactic heavy-particle radiotherapy may be a valuable treatment modality for surgically inaccessible intracranial AOVMs.

Delayed CNS radiation injury was studied with magnetic resonance imaging (MRI) and positron emission tomography (PET) in the rabbit brain using 225 keV X-rays (60 Gy) and 230 MeV/u Bragg peak helium ions (15 and 30 Gy) to the left hemisphere. MRI at 2.5 months after X-irradiation showed increased signal on T2-weighted images and T1-weighted gadolinium(Gd)-DTPA contrast enhancement indicating increased tissue water content and blood-brain barrier (BBB) breakdown. Regional cerebral blood flow (rCBF) was reduced in the irradiated hemisphere. The 15 Gy helium irradiated cases showed no alterations on imaging studies. The 30 Gy cases showed alterations at 9–11 months including high signal on T2-weighted MR images and enhancement on Tl-weighted Gd-DTPA MR images, primarily in the central white matter tracts and thalamus. These regions also showed reduced glucose utilization, measured by [18]FDG PET, and breakdown of the BBB, identified by [82]Rb PET. Histopathology showed white matter de-myelination and edema corresponding to high signal changes on T2-weighted MRI and cystic necrosis with gliosis and dilated blood vessels in the thalamus, corresponding to Gd-DTPA contrast enhancement and [82] Rb PET. Cerebrovascular effects with BBB breakdown and tissue edema or necrosis may be a final common pathway for both “early delayed” CNS injury from high dose X-ray exposure and “late delayed” injury from heavy charged particle (helium) irradiation.

Purpose: To devise a multiobjective optimization (MOO) method for IMRT that would provide a decision maker with a small set of well‐distributed Pareto optimal plans. Method and Materials: A multiobjective genetic algorithm was used; the fitness function was evaluated by a deterministic algorithm that consisted of a quadratic (BOXCQP: box constrained quadratic programming) and a non‐quadratic component. Each generation consisted of 10 individuals; the chromosome consisted of the OAR objective dose parameters. For the head and neck case studied, there were 6 objectives including maximum and mean dose objectives. For each individual, the deterministic algorithm was used to calculate beamlet intensities. OAR doses are variables in multiobjective GA and the target dose was fixed to 100%. The fitness function contained terms to minimize the difference between the OAR dose for adequate target coverage and the OAR dose goal and to minimize the dose goal for each OAR. Selection and breeding strategies were designed to provide a diverse population of individuals. Results: The algorithm was set to terminate after 100 generations or after five successive generations of no change in fitness. We compared genotypic and phenotypic distance functions and found that the phenotype provided better distribution of final plans. The decision making component was a Bayesian network coupled with a Markov cohort simulation to compute quality adjusted life expectancy and to rank plans accordingly. A set of optimal plans were also generated by varying the weighting factors for a fixed set of parameters but the distribution of plans was not as good. Conclusion: A genetic algorithm was designed to provide a diverse set of Pareto optimal solutions to the multiobjective optimization problem of IMRT inverse planning. The dose parameters in dosimetric objective functions were the variables in the optimization. The algorithm provided a well‐distributed set of plans for input to the Bayesian network.

Purpose: To develop the decision making component of a multiobjective IMRT optimization procedure for prostate cancer that incorporates disparate sources of information used in clinical decision making, the uncertain outcomes inherent in radiation therapy and the preferences of the patient. Method and Materials: Currently, many IMRT plans are developed for each patient without indication of which plan provides the optimal balance between tumor control and complication probability. Coupled with the typical number of objectives, plan selection is difficult. We chose a Bayesian Network (BN) coupled with a MarkovModel (MM) and utility theory to calculate Quality Adjusted Life Expectancy (QALE) for IMRTtreatment of prostate cancer. The BN was constructed with the advice of experts; conditional probabilities were obtained from research and clinical trial publications and expert opinion. Local, regional, and distant control were included as were complications to bladder and rectum. The MM relied on transition probabilities derived from the BN, published clinical trials and life expectancy tables. Utilities were obtained from the literature. Plan ranking was based on QALE or any of the components, e.g. local control or complications. Results: Probabilities of local and distant control as a function of disease state matched published values well, as did life expectancies. Sensitivity analyses highlighted the critical nodes in the network. Analysis of outcomes versus probability of lymph node involvement provided a basis for decisions regarding pelvic irradiation. A BN is well‐suited to handle rigorously conditional probabilities and the disparate nature of clinical variables. QALE provides a method for ranking plans based on clinically relevant criteria that incorporates the probabilistic nature of the outcome. Conclusion: A decision aid was constructed using a Bayesian Network coupled to a MarkovModel. This resulted in the ability to rank competing plans based either on QALE or specific outcomes.

Recent interest in stereotactic radiosurgery of intracranial lesions, and the development of stereotactic irradiation techniques has led to the need for a systematic and complete comparison of these methods. A method for conducting these comparisons is proposed and is applied to a set of currently-used stereotactic radiosurgical techniques. Three-dimensional treatment planning calculations are used to compare dose distributions for several different radiation types and irradiation geometries. Calculations were performed using charged particles (H, He, C, and Ne ions) and the irradiation geometry currently used at Lawrence Berkeley Laboratory. Photons in the Gamma Knife configuration and the Heidelberg Linac arc method are used. The 3-dimensional dose distributions were evaluated by means of dose-volume histograms and integral doses to the target volume and to normal brain. The effects of target volume, shape and location are studied. The charged particle dose distributions are more favorable than those of the photon methods. The differences between charged particles and photons increase with increasing target volume. The differences between different charged particle species are small, as are the effects of target shape and location.

Purpose: To investigate the use of [F‐18] fluoromisonidazole (FMISO) PET and intensity modulated radiation treatment(IMRT) planning to escalate the dose to hypoxic subvolumes in patients with advanced head and neck tumors.Method and Materials: Seventy‐three patients with head and neck cancer underwent FMISO‐PET scans, with fifty‐three of them also undergoing FDG‐PET scans as part of ongoing research studies. An initial treatment plan used a PTV defined with a 0.5‐cm margin around physician‐defined primary GTVs and affected nodal systems. The prescription dose is 70 Gy to the PTV and 50 Gy to the affected nodes, while sparing the spinal cord, mandible, and parotid glands. Physician‐defined regions of enhanced FMISO signal were used to define boost volumes on coregistered FMISO‐PET/CT images. The boost plan prescription dose to the hypoxic subvolumes is an additional 10 Gy. Results: Initial results from example treatment plans for two head and neck cancer patients are as follows (average over patients): to the PTV V100 = 87.2%, Dmin = 6081 cGy, D10 = 7303 cGy and to the nodal system V100 = 95.9%, Dmin = 4764 cGy, D10 = 5280 cGy. The IMRT boost plan yields V100 = 95.1%, Dmin = 979 cGy, D10 = 1012 cGy to the hypoxic PTV. The critical structures of interest received the following dose distributions from the composite IMRT plans: cord D1 = 3890 cGy, left (contralateral) parotid gland D1 = 1965 cGy, right parotid gland D1 = 4907 cGy (same side as primary tumor), and mandible D5 = 6220 cGy. Conclusion: We demonstrate the feasibility of directing dose‐escalatedIMRT to hypoxic subvolumes in head and neck cancer using coregistered FMISO‐PET and CTimages. Ongoing research and patient studies are expected to provide conclusive information on the clinical role of this procedure.

The workshop on grantsmanship will cover the required elements for writing a successful grant. Speakers will discuss the NIH grant review process, what reviewers look for, and how to get one's ideas across to the reviewers. There will be a focus on important strategies that successful grantees use in the grant preparation process and common mistakes in NIH grant applications to avoid. Following speaker presentations, a panel discussion will be held.

A method is described for stereotactic localization of intracranial arteriovenous malformations (AVM) and for calculating treatment plans for heavy charged-particle Bragg peak radiosurgery. A stereotactic frame and head immobilization system is used to correlate the images of multivessel cerebral angiography and computed tomography. The AVM is imaged by angiography, and the frame provides the stereotactic coordinates for transfer of this target to CT images for the calculation of treatment plans. The CT data are used to calculate the residual ranges and compensation for the charged-particle beam required for each treatment port. Three-dimensional coordinates for the patient positioner are calculated, and stereotactic radiosurgery is performed. Verification of the accuracy of the stereotactic postitioning is obtained with computer-generated overlays of the vascular malformation, stereotactic fiducial markers, and bony landmarks on orthogonal radiographs immediately prior to treatment. Using these procedures, the accuracy of the repositioning of the patient at each of a series of imaging and treatment procedures is typically within 1 mm in each of three orthogonal planes.

The p p elastic differential cross section at 30 GeV/c incident momentum has been measured in a two-arm spectrometer experiment (WA7) at the CERN SPS. The |t|-range covered extends from 0.5 to 5.8 (GeV/c)2. A pronounced dip-bump structure is observed, with a sharp minimum around |t| ≈ 1.7 (GeV/c)2. The results are compared with existing p p data at lower energies and with our earlier p p data at 50 GeV/c. A number of model predictions are discussed. We also compare the p p 30 GeV/c differential cross section with that of pp at the same momentum. Finally, the energy dependence of the p p fixed-|t| differential cross in the incident momentum range 3.6 to 50 GeV/c is presented.

Absolute electron excitation cross sections of the separate Zeeman states of the metastable 1s3 and 1s5 levels and the radiation-trapped 1s2 and 1s4 resonance levels of neon have been measured at an impact energy of 18.2 eV. The technique is based upon analysis of the polarisation of laser-induced fluorescence from the excited atoms. It is found that the cross sections for exciting the various Zeeman states belonging to the same 1s level are equal to one another within experimental error.

Biological research has established that air pollution can affect the yield and quality of agricultural crops. Economic assessments of crop exposure to air pollution have focused on the yield effect. This study illustrates the implications of considering crop quality effects in addition to crop yield changes for the case of O3 impacts on soybeans. An economic model of US soybean, soybean oil, and soybean meal markets is used to simulate the impacts of increased soybean yields due to reduced O3 concentrations with and without changes in soybean quality. The simulations with quality effects are richer in their distributional implications and show larger increases in economic surplus than the simulations with yield effects only.

The increasingly zealous support today for diversion of youth from the juvenile justice system is a consequence of several widely held notions: ( 1) Traditional strategies for dealing with juvenile offenders have not worked; ( 2) informal diversion is used both widely and effectively now; and ( 3) the most humane treatment of troubled youth is based upon the parens patriae philosophy of justice. Yet, the authors contend, diversion may be seen as potentially dangerous and harmful, and they present several arguments against expansion of diversionary services: (1) The concept's ambiguity allows many to promote expansion of the juvenile justice system in the form of diversion "to" other programs, while true diversion "from" the system is nonexistent; ( 2) the goals of diversionary programs-such as elimination of stigmatizing labels and formal duplica tion of existing informal processes-are unattainable; ( 3) formal diversion is incompatible with due process ideals. Until these difficulties have been resolved, diversionary options should be viewed with caution.

A measurement of the proton-proton elastic differential cross section at 50 GeV/ c incident momentum in the momentum transfer range 0.8 t | c ) 2 is presented. The data are compared to pp data at lower and higher energies, and to some model predictions.

A unique approach which combined anthropometric data, human anatomical models, and artistic renderings was used to synthesize male and female manikin models representing the U.S. general population. The derivation of dimensions, joint locations and reach envelopes are discussed and scale drawings of the 5th percentile female and 15th percentile male manikins are presented. These manikins were used to derive console ergonomic requirements for next-generation air traffic controller workstations.

Among the manuscripts of the Biblioteca Nazionale in Florence there is a copy of an extensive eyewitness account of Florentine politics in the 1460's which appears to have been overlooked by historians of Florentine politics and historiography. Catalogued as Magliabecchi xxv, 272, it is described as an anonymous sixteenth-century manuscript containing ‘Diverse notizie istoriche d'Italia, delle potenze che la dominavano nel 1464 e delle cose seguite in Firenze contro la fazione de’ Medici fino al 1467.’ Although the manuscript is not a fifteenth-century autograph, there can be little doubt as to the authenticity of its contents. Not only does it contain a considerable amount of specific information that could only come from a firsthand source, but several self-references make it apparent that it is the work of the silk merchant and humanist Marco Parenti.

The application of heavy charged particle Bragg peak radiosurgery for the treatment of intracranial vascular and other disorders requires a system of precise patient immobilization and stereotactic localization of defined intracranial targets. The process of using stereotactic neuroradiological procedures (including cerebral angiography, CT scanning and magnetic resonance imaging) for target definition and localization, and complex treatment planning constrain such a system to be adaptable and reusable. This paper describes a removable stereotactic frame-mask system that is used to immobilize and reposition the patient during stereotactic neuroradiological procedures and charged particle radiosurgery. It consists of four parts--(a) a plastic mask for immobilizing the patient's head; (b) a lucite-graphite mounting frame; (c) a set of fiducial markers; and (d) interfaces between the frame for immobilization and fixation to various diagnostic and therapeutic patient couches. The relationship between each component and the radiosurgical procedure is discussed. This system has proven to be safe, reliable, and noninvasive and it does not require fixation to the bones of the face or skull. When integrated into the radiosurgical treatment planning and localization procedures developed at Lawrence Berkeley Laboratory, it is capable of reliably repositioning the patient to 1 mm in each of three planes and contouring the intracranial target reliably to this accuracy. The application of this stereotactic system in heavy charged particle radiosurgery of intracranial arteriovenous malformations is described in other reports.

A method is described for stereotactic localization of intracranial arteriovenous malformations (AVM) and for calculating treatment plans for heavy charged-particle Bragg peak radiosurgery. A stereotactic frame and head immobilization system is used to correlate the images of multivessel cerebral angiography and computed tomography. The AVM is imaged by angiography, and the frame provides the stereotactic coordinates for transfer of this target to CT images for the calculation of treatment plans. The CT data are used to calculate the residual ranges and compensation for the charged-particle beam required for each treatment port. Three-dimensional coordinates for the patient positioner are calculated, and stereotactic radiosurgery is performed. Verification of the accuracy of the stereotactic postitioning is obtained with computer-generated overlays of the vascular malformation, stereotactic fiducial markers, and bony landmarks on orthogonal radiographs immediately prior to treatment. Using these procedures, the accuracy of the repositioning of the patient at each of a series of imaging and treatment procedures is typically within 1 mm in each of three orthogonal planes.

Twenty-four patients with intracranial vascular malformations were examined before and after helium ion radiosurgical treatment with angiography, computed tomography (CT), and magnetic resonance (MR) imaging. Twenty patients had high-flow arteriovenous malformations (AVMs). After treatment 18 of 20 AVMs (90%) showed a significant reduction in size on angiograms or MR images. Eleven of 20 (55%) had complete resolution on angiograms or MR images, 35% had partial resolution, and 10% showed no size change. Before treatment, the size range of the AVMs was 0.86-383 cm3 (median, 21.7 cm3). Smaller AVMs (less than 8 cm3) were more likely to resolve completely than medium-sized AVMs (8-64 cm3) or larger AVMs (greater than 64 cm3). Four additional patients had slow-flow vascular malformations: One had a venous angioma; one, a probable cavernous hemangioma; and two, malformations that were not seen on angiograms. CT proved inaccurate in demonstrating the boundaries of the AVM after treatment because it showed persistent contrast enhancement even when the AVM was completely obliterated on angiograms. MR imaging and angiography were complementary in the evaluation of therapeutic results and should be the primary modalities in the examination of patients with AVMs.

Malignant giant cell tumors of the pancreas are rare neoplasms which have been generally thought to represent epithelial malignancies of either acinar or ductal epithelium. The authors have studied a tumor of the pancreas that was characterized histologically by a proliferation of benign-appearing osteoclast-type giant cells in association with atypical, often bizarre mononuclear cells. Immunohistochemical studies demonstrated negative staining of the tumor cells with epithelial markers, including low-molecular weight keratins, carcinoembryonic antigen and epithelial membrane antigen, and positive staining with vimentin antibodies, supporting a fibroblastic line of differentiation. Electron microscopic examination also showed absence of ultrastructural features of epithelial differentiation such as microvilli, intercellular junctions, or desmosomes. The authors believe the current case represents a true sarcoma of the pancreas, currently best classified as a malignant fibrous histiocytoma, giant cell type. This tumor should be distinguished from the epithelial type of osteoclastic giant cell tumor of the pancreas.

The program at Donner Pavilion has applied nuclear medicine research to the diagnosis and radiosurgical treatment of life-threatening intracranial vascular disorders that affect more than half a million Americans. Stereotactic heavy-charged-particle Bragg peak radiosurgery, using narrow beams of heavy ions, demonstrates superior biological and physical characteristics in brain over X-and γ-rays, viz., improved dose distribution in the Bragg peak and sharp lateral and distal borders and less scattering of the beam. Examination of CNS tissue response and alteration of cerebral blood-flow dynamics related to heavy-ion Bragg peak radiosurgery is carried out using three-dimensional treatment planning and quantitative imaging utilizing cerebral angiography, computerized tomography (CT), magnetic resonance imaging (MRI), cine-CT, xenon X-ray CT and positron emission tomography (PET). Also under examination are the physical properties of narrow heavy-ion beams for improving methods of dose delivery and dose distribution and for establishing clinical RBE/LET and dose-response relationships for human CNS tissues. Based on the evaluation and treatment with stereotactically directed narrow beams of heavy charged particles of over 300 patients, with cerebral angiography, CT scanning and MRI and PET scanning of selected patients, plus extensive clinical and neuroradiological followup, it appears that Stereotactic charged-particle Bragg peak radiosurgery obliterates intracranial arteriovenous malformations or protects against rebleeding with reduced morbidity and no mortality. Discussion will include the method of evaluation, the clinical research protocol, the Stereotactic neuroradiological preparation, treatment planning, the radiosurgery procedure and the protocol for followup. Emphasis will be placed on the neurological results, including the neuroradiological and clinical response and early and late delayed injury in brain leading to complications (including vasogenic edema, arterial occlusion, venous thrombosis and radiation necrosis). Clinical results in both children and adults will be illustrated and health outcome will be related to the advantages of charged-particle treatment planning, the radiosurgical procedure, dose distribution and dose localization.

Principles and techniques derived from Gestalt therapy are being applied in a variety of educational settings internationally. These pioneering efforts in applying Gestalt to education have been taking place through the Confluent Education Program at the University of California, Santa Barbara, and have focused on a number of broad objectives with respect to teacher personality, teacher skills, and written curriculum. Initial investigations of the results of these applications have noted significant increases in teachers' self-knowledge, sense of personal control, flexibility, and attention to the "here and now." Addi tionally, students in confluent classrooms have shown significant increases in a number of areas, including self-esteem and self-awareness.

Forty patients aged 6 to 18 years have now been treated for inoperable intracranial arteriovenous malformations (AVMs) using stereotactic heavy-charged-particle Bragg peak radiosurgery at the Lawrence Berkeley Laboratory 184-inch Synchrocyclotron at the University of California, Berkeley. This paper describes the procedures for selection of patients, the treatment protocol, and the neurological and neuroradiological responses to stereotactic radiosurgery in this age group. The volumes of the treated AVMs ranged from 265 mm3 to 60,000 mm3. The results are favorable: thus far, 20 of 25 patients have experienced ≥50% obliteration of their AVMs within 1 year after treatment, and 14 of 18 patients have experienced total obliteration of the AVM by 2 years after treatment. Two patients hemorrhaged from radiosurgically treated AVMs within 12 months after treatment, but none thereafter. Complications include vasogenic edema and arterial occlusion; three patients have had neurological worsening as definite or possible sequelae of treatment. The strengths and limitations of the method are discussed.