A clinical interactive technique for MR-CT image registration for target delineation of intracranial tumors.

Replacement of current CT-based, three-dimensional (3D) treatment planning systems by newer versions capable of automated multi-modality image registration may be economically prohibitive for most radiation oncology clinics. We present a low-cost technique for MR-CT image registration on a "first generation" CT-based, 3D treatment planning system for intracranial tumors. The technique begins with fabrication of a standard treatment mask. A second truncated mask, the "minimask," is then made, using the standard mask as a mold. Two orthogonal leveling vials glued onto the minimask detect angular deviations in pitch and roll. Preservation of yaw is verified by referencing a line marked according to the CT laser on the craniocaudal axis. The treatment mask immobilizes the patient's head for CT. The minimask reproduces this CT-based angular treatment position, which is then maintained by taping the appropriately positioned head to the MR head coil for MR scanning. All CT and MR images, in DICOM 3.0 format, are entered into the treatment planning system via a computer network. Interactive registration of MR to CT images is controlled by real-time visual feedback on the computer monitor. Translational misalignments at the target are eliminated or minimized by iterative use of qualitative visual inspection. In this study, rotational errors were measured in a retrospective series of 20 consecutive patients who had undergone CT-MR image registration using this technique. Anatomic structures defined the three CT orthogonal axes from which angular errors on MR image were measured. Translational errors at the target isocenter were within pixel size, as judged by visual inspection. Clinical setup using the minimask resulted in overall average angular deviation of 3 degrees +/-2 degrees (mean +/- SD) and translational deviation within the edges of the target volume of typically less than 2 mm. The accuracy of this registration technique for target delineation of intracranial tumors is compatible with practice guidelines. This method, then, provides a cost-effective means to register MR and CT images for target delineation of intracranial tumors.

Potential pitfalls in the use of Glucoscan and Glucoscan II meters for self-monitoring of blood glucose.

We discovered that skilled nurses only casually trained in the use of a fingertip blood glucose reflectance meter (Glucoscan, Lifescan, Mountainview, California) had a 36% incidence of unacceptable results (greater than 15% from reference). A controlled study was undertaken and showed that with Glucoscan I (GI) 4 of 27 readings were unacceptable and with Glucoscan II (GII) 3 of 27 readings were unacceptable, a statistically nonsignificant difference. Minor deviations from the manufacturer's recommended technique had a significant effect on the results with GI. In contrast, GII was much less sensitive to variations in recommended technique. GI underestimated the reference glucose concentration by 11.7%, and GII overestimated by 6.5%, a statistically significant difference. We conclude that the health professional must be aware of interdevice and intradevice variability in self-monitoring of blood glucose (SMBG). Patients need careful training in the method of SMBG. The results of any single value should be interpreted with caution.

Hemophilus influenza infection of an implantable insulin-pump pocket.

OBJECTIVE: To increase awareness of adverse events associated with the use of implantable insulin pumps. RESEARCH DESIGN AND METHODS: A descriptive case report of a pump implant infection. RESULTS: This is a case report of one implanted insulin pump-pocket infection among a series of 15 patients. After exposure to a child with a respiratory infection on PID 30, V.L.C. (the patient) developed a fulminant pump-pocket infection. H. influenza was recovered from it. Despite aggressive antibiotic therapy, the infection could not be controlled. Insulin delivery ceased, and the pump was explanted. The pump-pocket infection rapidly resolved with pump removal, permitting later reimplantation. CONCLUSIONS: We have adopted the American Heart Association indications and antimicrobial prophylaxis regimens recommended for prevention of endocarditis in patients with prosthetic values for patients with implanted insulin pumps.

Heavy charged-particle stereotactic radiosurgery: cerebral angiography and CT in the treatment of intracranial vascular malformations.

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 positioning 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.

Comparison of different radiation types and irradiation geometries in stereotactic radiosurgery.

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.

Image correlation of MRI and CT in treatment planning for radiosurgery of intracranial vascular malformations.

Magnetic resonance imaging (MRI) has been incorporated with stereotactic cerebral angiography and computed tomography (CT) in the treatment planning process of heavy ion radiosurgery of intracranial arteriovenous malformations (AVM's). Correlation of the images of the AVM and normal tissue on each of these neuroradiological imaging modalities is achieved by means of fiducial markers. The computerized transfer of angiographic information to the CT images regarding the size, shape, and location of the abnormal vasculature has been described in an earlier report. A separate computer program calculates a fit between individual fiducial markers on the CT and MR images that enables the transfer of contours between the two imaging modalities. The MR images aid in the determination of the 3-dimensional shape of the AVM, adding to the information derived from the two angiographic projections. Currently, MRI cannot replace cerebral angiography in delineating the entire arterial phase of the AVM. Magnetic resonance imaging is invaluable in the treatment planning of angiographically-occult AVM's, determining the location, size, and shape of the volume to be treated. Correlation of the CT and MRI images allows for the transfer of CT-calculated isodose contours to the MRI images to aid in the determination of optimal treatment plans.

Computed tomography slice-by-slice target-volume delineation for stereotactic proton irradiation of large intracranial arteriovenous malformations: an iterative approach using angiography, computed tomography, and magnetic resonance imaging.

PURPOSE: Target-volume delineation for stereotactic irradiation is problematic for large and irregularly shaped arteriovenous malformations (AVMs). The purpose of this report is to quantify modifications in the target volume that result from iterative treatment planning that incorporates multimodality imaging data. METHODS AND MATERIALS: Stereotactic neuroimaging procedures were performed for 20 consecutive patients with AVM volumes > 10 cm3. Angiographically defined extrema were transformed into computed tomography (CT) space. The resulting target contours were then modified by a multidisciplinary treatment planning team after iterative review of angiographic, CT, and magnetic resonance imaging (MRI) data. Volumes of interest and dose-volume histograms for proton irradiation were calculated before and after iterative target delineation. RESULTS: Initial (angiographically defined) target volumes ranged from 15.3 to 96.1 cm3 (mean, 43.6 cm3). Final (iteratively defined) target volumes ranged from 10.7 to 114.0 cm3 (mean, 38.4 cm3). The volume of presumed normal tissue excluded by iterative planning ranged from 2.6 to 47.0 cm3 (mean, 15.5 cm3). Initially untargeted AVM, most commonly obscured by embolization material, was identified in all cases (range, 0.3 to 57.8 cm3; mean, 10.3 cm3). Corresponding dose-volume histograms demonstrated marked differences regarding lesion coverage and sparing of normal tissue structures. CONCLUSIONS: Iterative target-volume delineation resulted in significant modifications from initial, angiographically defined target volumes. Substantial amounts of apparently normal tissue were excluded from the final target, and additional abnormal vascular structures were identified for incorporation. We conclude that an iterative multimodality approach to target-volume delineation may improve the overall results for stereotactic irradiation of large and complex AVMs.

Serum thyroid hormone abnormalities in psychiatric disease.

Psychiatric illness is a cause of "euthyroid sick syndrome" (ESS), defined as abnormal concentrations of circulating iodothyronines in euthyroid subjects with nonthyroidal illness (NTI). We describe a prospective study of 150 consecutive psychiatric admissions studied by endocrine and psychologic techniques. Based on 150 admission blood samples, we found a 7% incidence of ESS and with serial samples (74 patients) the incidence was 27%, demonstrating that ESS can develop after hospital admission. Of the 20 patients with ESS, 11 had elevation of both serum total T4 concentrations (T4) and free thyroxine index (FTI) while their serum total T3 concentrations (T3) remained normal; 5 had elevation of FTI without elevation of T4 or T3; and 4 had low T4 and low FTI and normal TSH. In 2 of the 4 patients in the last category, the T3 was also low. The free T3 index (FT3I) was normal in all but 1 patient who had low FT3I and FTI, low T4 and T3, and normal TSH. The serum thyroid hormone abnormalities were transient in the ESS patients during the 10 day period with 2 exceptions; 1 patient had persistently elevated T4 and FTI with normal T3 and FT3I values while another patient had persistently depressed T4 and FTI without abnormality of FT3I or TSH. Multivariate statistical analysis demonstrated a difference (P less than .06) in the psychologic attributes of somatic and autonomic symptoms in ESS patients compared to controls. We conclude that ESS is as common amongst psychiatric admissions as in general hospital patients previously studied and that blood thyroid function tests should be interpreted cautiously in all hospitalized patients.

Endovascular treatment of cerebral arteriovenous malformations following radiosurgery.

PURPOSE: Previous reports of embolization of cerebral arteriovenous malformations (AVMs) have evaluated the technique as adjunctive therapy prior to surgery or radiosurgery; our aim is to assess the role of embolization following radiosurgery. PATIENTS: Six patients previously treated with radiosurgery and showing no response as judged by cerebral angiography were embolized 24 to 55 months (mean 34.3 months) after initial radiosurgery. RESULTS: In five of six, a significant volume reduction was achieved ranging from 60%-100% (mean 74%). One patient was treated with embolization alone and the AVM has remained fully thrombosed 2 years after treatment. Three patients underwent surgical resection for cure after embolization, and two patients had repeat radiosurgery to a significantly smaller AVM volume. One patient had an asymptomatic carotid dissection at embolization; however, no clinically apparent complications occurred in the treatment group. CONCLUSION: Embolization can be used after radiosurgery to assist in the management of those AVMs that have not responded to initial treatment.

Pathological changes in surgically resected angiographically occult vascular malformations after radiation.

OBJECTIVE: The goal of this study was to evaluate the pathological changes associated with radiation treatment (stereotactic radiosurgery or conventional irradiation) of angiographically occult vascular malformations (AOVMs). METHODS: Eleven patients underwent surgical resection of an AOVM in the mesial temporal lobe, brain stem, thalamus, or basal ganglia after previous radiation treatment. The indications for surgery were recurrent symptomatic bleeding from the lesion in 10 patients and recurrent intractable seizures in 1 patient. Radiation was used as the initial therapy because the risk of surgical resection was deemed too high. Three patients received conventional radiation therapy of 3000 to 5400 rads at an outside institution. One patient received radiosurgery with the gamma knife at another institution using a dose of 15 Gy to the margin. The remaining 7 patients received stereotactic radiosurgery with a helium-ion particle beam. The dose range was from 18 to 26 Gy equivalents. The interval from radiation to surgical resection ranged from 1 to 10 years, with a mean of 3.5 years. These lesions were compared with 10 nonirradiated cavernous malformations. RESULTS: One irradiated lesion was identified pathologically as a true arteriovenous malformation despite being angiographically occult. This lesion did not demonstrate significant changes in the vasculature but did have radiation necrosis of the surrounding brain 5 years after 25 Gy equivalents of helium-ion radiosurgery. Two other specimens were too small to identify the type of vascular malformation adequately. Of the remaining eight malformations identified as cavernous malformations, six showed a combination of marked fibrosis of the vascular channels, fibrinoid necrosis, and ferrugination. However, the fibrinoid necrosis was the only finding unique to the irradiated lesions compared with nonirradiated controls. All the irradiated lesions still had patent vascular channels; none were completely thrombosed. CONCLUSION: Radiosurgery or conventional radiation therapy did not cause histologic vascular obliteration in intracranial AOVMs evaluated 1 to 10 years (mean 3.5 yr) after radiation delivery. It should be recognized that these patients are irradiation failures who may not be representative of all irradiated patients. However, recurrent bleeding from AOVMs may relate to poor radiation response in some patients.

Stereotactic heavy-charged-particle Bragg peak radiosurgery for the treatment of intracranial arteriovenous malformations in childhood and adolescence.

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 greater than or equal to 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.

The management of patients with arteriovenous malformations and associated intracranial aneurysms.

OBJECTIVE: Few published studies have focused specifically on the unique management issues encountered in treating patients with arteriovenous malformations (AVMs) and associated intracranial aneurysms. The primary objective of this study was to retrospectively review the clinical and radiographic features of these patients. METHODS: Medical records of all patients seen at Stanford University Hospital between 1988 and 1996 with a diagnosis of AVMs were retrospectively reviewed. Aneurysms were identified by conventional angiography and characterized by size, number, and location relative to the AVMs. AVMs were graded according to the Spetzler-Martin scale. Odds ratios were calculated for the risk of intracranial hemorrhage. Variables included age, sex, number of aneurysms, and AVM grade. RESULTS: Forty-five of 600 patients (7.5%) were identified as having coexisting intracranial aneurysms. All 45 patients had high-flow malformations, and 58% had AVMs of Spetzler-Martin Grade IV or higher. A majority of patients had multiple aneurysms. There was a statistically significant increase in AVM hemorrhage in female patients (odds ratio, 8.53 [1.87-38.98]; P < 0.005). There was no statistically significant correlation between the development of hemorrhage and either age, AVM grade, or the number of aneurysms. Twenty-three patients (51%) presented with intracranial hemorrhage: bleeding occurred from the AVMs in 15 and from ruptured aneurysms in 5, and the source of the bleeding could not be determined in 3. Overall, nine patients (20%) bled from ruptured aneurysms: five at presentation, two during or within 3 weeks of AVM treatment, and two from new aneurysms. Two of these nine patients died as a direct result of aneurysmal subarachnoid hemorrhage. Five patients (11%) developed new aneurysms. CONCLUSION: Aneurysms associated with AVMs are at risk for rupture before, during, and immediately after treatment of the AVMs. New aneurysms may arise in patients with high-flow AVMs. The risk of intracranial hemorrhage from either source is higher in female patients. To reduce the complications of intracranial hemorrhage in these patients, we recommend a management protocol designed to treat the aneurysms by surgical or endovascular means before administering definitive therapy for the AVMs. Meticulous intraoperative blood pressure control and fluid management during aneurysm surgery is critical to avoid hemorrhage from the AVMs.

An experimental compartmental flow model for assessing the hemodynamic response of intracranial arteriovenous malformations to stereotactic radiosurgery.

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.

Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience.

OBJECTIVE: Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment. METHODS: All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr). RESULTS: Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery). CONCLUSION: Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.

Surgical resection of large incompletely treated intracranial arteriovenous malformations following stereotactic radiosurgery.

Although radiosurgery is effective in obliterating small arteriovenous malformations (AVMs), it has a lower success rate for thrombosing larger AVMs. The authors surgically resected AVMs from 33 patients ranging in age from 7 to 64 years (mean 30.4 years) 1 to 11 years after radiosurgery. Initial AVM volumes were 0.8 to 117 cm3 (mean 21.6 cm3), and doses ranged from 4.6 to 45 GyE (mean 21.2 GyE). Of 27 AVMs in eloquent or critical areas, 10 were located in language, motor, sensory, or visual cortex, 11 in the basal ganglia/thalamus, one each in the brainstem, hypothalamus, and cerebellum, and three in the corpus callosum. Venous drainage was deep in 13, superficial in 12, or both in eight lesions. Spetzler-Martin grades were II in one, III in 12, IV in 16, and V in four patients. Eight patients experienced rebleeding after radiosurgery but prior to surgery. Three patients developed radiation necrosis and 25 underwent endovascular embolization prior to surgery. At surgery the AVMs were found to be markedly less vascular, partially thrombosed, and more easily resected, compared to those seen in patients who had not undergone radiosurgery. Pathological investigation showed endothelial proliferation with hyaline and calcium in vessel walls. There was partial or complete thrombosis of some AVM vessels and evidence of vessel and brain necrosis in many cases. Complete resection was achieved in 28 patients and partial resection in five. Clinical outcome was excellent or good in 31 cases, and two patients died of rebleeding from residual AVM. Four patients' conditions worsened following microsurgical resection. Final clinical outcome was largely related to the pretreatment grade. Radiosurgery several years prior to open microsurgery may prove to be a useful adjunct in treating unusually large and complex AVMs.

Dosimetry techniques for narrow proton beam radiosurgery.

Characterization of narrow beams used in proton stereotactic radiosurgery (PSRS) requires special efforts, since the use of finite size detectors can lead to distortion of the measured dose distributions. Central axis depth doses, lateral profiles and field size dependence factors are the most important beam characteristics to be determined prior to dosimetry calculations and beam modelling for PSRS. In this paper we report recommendations for practical dosimetry techniques which were developed from a comparison of beam characteristics determined with a variety of radiation detectors for 126 and 155 MeV narrow proton beams shaped with 2-30 mm circular brass collimators. These detectors included small-volume ionization chambers, a diamond detector, an Hi-p Si diode, TLD cubes, radiographic and radiochromic films. We found that both types of film are suitable for profile measurements in narrow beams. Good agreement between depth dose distributions measured with ionization chambers, diamond and diode detectors was demonstrated in beams with diameters of 20-30 mm. The diode detector can be used in smaller beams, down to 5 mm diameter. For beams with diameters less than 5 mm, reliable depth dose data may be obtained only with radiochromic film. The tested ionization chambers are appropriate for calibration of beams with diameters of 20-30 mm. TLD cubes and diamond detectors are useful to determine relative dose in beams with diameters of 10-20 mm. Field size factors for smaller beams should be obtained with diode and radiochromic film. We conclude that dosimetry characterization of proton beams down to several millimetres in diameter can be performed using the described procedures.

Stereotactic radiosurgery of arteriovenous malformations: pathologic changes in resected tissue.

Both stereotactic radiosurgery and microsurgery are treatment modalities for arteriovenous malformations (AVM), and more recently, multimodality treatment using these approaches has been utilized. We surgically resected AVMs from 33 patients (ages 7-64 years old, mean age 30.4) 1-11 years after radiosurgery. AVM volumes were 0.8-117 cm3 (mean 21.6 cm3), and doses ranged from 4.6-45 GyE (mean 21.2 GyE). AVMs resected were submitted for pathologic review. Each AVM was evaluated for the following radiation changes, and the number of AVMs demonstrating these changes were noted: endothelial proliferation (27), hyaline (18) and calcium (10) in AVM vessel walls, partial (9) or complete (24) thrombosis of some AVM vessels, and necrosis of vessels (15) and adjacent brain tissue (11). A semiquantitative scale (mild, moderate, severe) incorporating the aforementioned changes present in each case classified the extent of radiation-induced change. There was a significant correlation (r = 0.624, p < 0.01) between extent of radiation change and dose of radiation received. There was no absolute radiation dose threshold below which radiation-induced changes were absent. However, all but one patient receiving greater than 20 GyE developed moderate to severe radiation vascular changes and the 3 patients treated with greater than 30 GyE all had severe radiation-induced changes. Radiation changes in AVMs following stereotactic radiosurgery appear to be dose-related. The correlation of dose to extent of radiation change may allow the determination of the optimal dose of radiation to treat AVMs.

Radiation physics for particle beam radiosurgery.

For the particles and energies considered suitable for radiosurgery, with increasing particle charge, the Bragg peak height reaches a maximum with helium and then decreases, the Bragg peak width narrows, the distal fall-off steepens, and the exit dose increases (Table 1). The helium-ion beam is superior to a proton beam because of the higher peak-plateau ratio, more rapid dose fall-off, and smaller beam deflection, and it suffers only in the modest exit dose. Comparison of the therapeutically useful parameters of these beams is complicated by the change in beam quality (LET) with depth. Considerations of RBE values, which change with the ion species and with depth of penetration, may alter the relative rankings based on one or more of these beam characterization values. For all these beams, the RBE increases with increasing LET. The effect for protons is small and occurs just at the end of range of the particles. Effective isodose distributions based on modeled beams have been reported for helium, carbon, and neon ions. These distributions include the effects of a varying RBE with changes in the beam quality (as measured by a dose-weighted LET) and the change in dose fraction size with depth (the dose per fraction is a function of the depth of penetration). These calculations suggest that the optimal charged-particle beam for radiosurgery might be carbon. Heavy charged-particle beams can produce dose distributions superior to those obtainable with photon or electron beams. In clinical trials, these dose distributions have proved to be useful for the treatment of human diseases, including neoplasia and life-threatening intracranial disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Charged-particle radiosurgery of the brain.

Charged-particle beams (e.g., protons and helium, carbon and neon ions) manifest unique physical properties which offer advantages for neurosurgery and neuroscience research. The beams have Bragg ionization peaks at depth in tissues, and finite range and are readily collimated to any desired cross-sectional size and shape by metal apertures. Since 1954 nearly 6000 neurosurgical patients worldwide have been treated with stereotactic charged-particle radiosurgery of the brain for various localized and systemic malignant and nonmalignant disorders. Experimental studies with charged-particle beams have been carried out in laboratory animals to characterize anatomic and physiologic correlates of various behavioral and functional properties in the brain. Highly focused charged-particle beams have been used to induce sharply delineated laminar lesions or discrete focal ablation of deep-seated brain structures for the study of the functional anatomy of selected intracranial sites. Charged-particle beam irradiation for stereotactic radiosurgery and radiation oncology of intracranial disorders has achieved increasing importance internationally. More than 30 biomedical accelerator facilities on four continents are currently fully operational, under construction, or in an active planning stage; this last group consists primarily of dedicated biomedical hospital-based facilities. Therapeutic efficacy has been demonstrated clearly for the treatment of selected intracranial sites, e.g., pituitary adenomas and intracranial arteriovenous malformations. Heavier charged particles (e.g., carbon and neon ions) have been found to manifest a number of valuable radiobiologic properties and appear to be of potential advantage in the radiosurgical treatment of those primary or metastatic brain tumors that are radioresistant. The optimal dose and choice of charged-particle species must be determined for the treatment of the different intracranial disorders to improve the cure rate and to minimize potential adverse sequelae of the reaction of the brain to radiation injury.

Charged-particle radiosurgery for intracranial vascular malformations.

Heavy charged-particle radiation has unique physical characteristics that offer several advantages over photons and protons for stereotactic radiosurgery of intracranial AVMs. These include improved dose distributions with depth in tissue, small angle of lateral scattering, and sharp distal fall-off of dose in the Bragg ionization peak. Under multi-institutionally approved clinical trials, we have used stereotactic helium-ion Bragg peak radiosurgery to treat approximately 400 patients with symptomatic, surgically inaccessible vascular malformations at the UCB-LBL 184-in synchrocyclotron and bevatron. Treatment planning for stereotactic heavy charged-particle radiosurgery for intracranial vascular disorders integrates anatomic and physical information from the stereotactic cerebral angiogram and stereotactic CT and MR imaging scans for each patient, using computerized treatment-planning calculations for optimal isodose contour distribution. The shape of an intracranial AVM is associated strongly with its treatability and potential clinical outcome. In this respect, heavy charged-particle radiosurgery has distinct advantages over other radiosurgical methods; the unique physical properties allow the shaping of individual beams to encompass the contours of large and complexly shaped AVMs, while sparing important adjacent neural structures. We have had a long-term dose-searching clinical protocol in collaboration with SUMC and UCSF and have followed up over 300 patients for more than 2 years. Initially, treatment doses ranged from 45 GyE to 35 GyE. Currently, total doses up to 25 GyE are delivered to treatment volumes ranging from 0.1 cm3 to 70 cm3. This represents a relatively homogeneous dose distribution, with the 90% isodose surface contoured to the periphery of the lesion; there is considerable protection of normal adjacent brain tissues, and most of the brain receives no radiation exposure. Dose selection depends on the volume, shape, and location of the AVM and several other factors, including the volume of normal brain that must be traversed by the plateau portion of the charged-particle beam. The first 230 patients have been evaluated clinically to the end of 1989. Using the clinical grading of Drake, about 90% of the patients had an excellent or good neurologic grade, about 5% had a poor grade, and about 5% had progression of disease and died, or died as a result of unrelated intercurrent illness. Neuroradiologic follow-up to the end of 1989 indicated the following rates of complete angiographic obliteration 3 years after treatment: 90% to 95% for AVM treatment volumes less than 4 cm3, 90% to 95% for volumes 4 to 14 cm3, and 60% to 70% for volumes greater than 14 cm3.(ABSTRACT TRUNCATED AT 400 WORDS)