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Biomedical subjects

J M Slater

Publications and source records attributed to J M Slater.

At least 19 recordsLinked to original sources

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.

Brain Neoplasms↗

Hierarchy of regional oxygen delivery during cardiopulmonary bypass.

BACKGROUND: Relative to the nonbypass state, cardiopulmonary bypass may decrease whole-body oxygen (O2) delivery. We predicted that during cardiopulmonary bypass, a hierarchy of regional blood flow and O2 delivery could be characterized. METHODS: In 8 46.5 +/- 1.2-kg pigs, fluorescent microspheres were used to determine blood flow and O2 delivery to five organ beds before and during 37 degrees C cardiopulmonary bypass at four randomized bypass flows (1.4, 1.7, 2.0, and 2.3 L/min/m2). At completion, 18 tissue samples were obtained from the cerebral cortex (n = 4), renal cortex (n = 2), renal medulla (n = 2), pancreas (n = 3), small bowel (n = 3), and limb muscle (n = 4) for regional blood flow determination. RESULTS: At conventional cardiopulmonary bypass flow (2.3 L/min/m2), whole-body O2 delivery was reduced by 44 +/- 6% relative to the pre-cardiopulmonary bypass state (p < 0.05). Over a range of cardiopulmonary bypass flows (2.3 to 1.7 L/min/m2), brain and kidney maintained their perfusion. Blood flow and O2 delivery to both regions were reduced when the cardiopulmonary bypass flow was reduced to 1.4 L/min/m2. However, perfusion and O2 delivery to other visceral organs (pancreas, small bowel) and skeletal muscle showed pump flow dependency over the range of flows tested. CONCLUSIONS: This study characterizes the organ-specific hierarchy of blood flow and O2 distribution during cardiopulmonary bypass. These dynamics are relevant to clinical decisions for perfusion management.

Animals↗

Distribution and hierarchy of regional blood flow during hypothermic cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) may decrease oxygen delivery relative to the nonbypass state. We predicted that a hierarchy of regional blood flow could be characterized under hypothermic (27 degrees C) CPB. METHODS: Ten pigs underwent bypass at 27 degrees C. Fluorescent microspheres were administered before and during CPB at four randomized flows: 1.9, 1.6, 1.3, and 1.0 L x min(-1) x m(-2). At completion, tissue samples were obtained from brain, renal cortex and medulla, pancreas, small bowel, and limb muscle for regional blood flow determination. RESULTS: Cerebral blood flow remained unchanged between CPB flows of 1.9 and 1.3 L x min(-1) x m(-2). Renal perfusion was stable between flows of 1.9 and 1.6 L x min(-1) x m(-2), whereas perfusion of small bowel decreased linearly with pump flow. Pancreatic perfusion was unchanged over the range of flows studied; muscle blood flow was profoundly reduced at the highest CPB flow and further decreased if pump flow was reduced below 1.6 L x min(-1) x m(-2). CONCLUSIONS: This study characterizes the organ-specific hierarchy of blood flow and oxygen distribution during hypothermic CPB. These dynamics are relevant to clinical decisions for perfusion management.

Animals↗

Carbon dioxide management and the cerebral response to hemodilution during hypothermic cardiopulmonary bypass in dogs.

BACKGROUND: Increases in blood flow support oxygen (O2) delivery with hemodilution. However, with alpha-stat management, the cerebral response to hemodilution is blunted. We tested the hypothesis that carbon dioxide (CO2) management is a primary determinant of the cerebral blood flow (CBF) response to hemodilution during hypothermic bypass. METHODS: Following Animal Care Committee approval, 15 dogs underwent bypass at 18 degrees C (pH-stat, n = 7 or alpha-stat, n = 8). Measurements were obtained after progressive hemodilution, and cerebral blood flow was determined by sagittal sinus outflow. Arterial pressure was maintained at 60 to 70 mm Hg. The CBF response to hemodilution and cerebral metabolic rate were compared in the two groups of animals. RESULTS: In both groups, hemodilution increased CBF. At every hematocrit, CBF and O2 delivery in the pH-stat group exceeded that of alpha-stat group, although O2 demand did not differ between groups. While absolute CBF in the pH-stat group was greater at every hematocrit, the relative change in CBF from control and the slope of the CBF-Hct relationship did not differ between groups. CONCLUSIONS: pH-stat management is associated with a greater absolute CBF and a greater ratio of cerebral O2 supply to demand for any degree of hemodilution. However, over the range of hematocrits common in practice, CO2 management per se does not determine the cerebral response to hemodilution.

Animals↗

Effects of proton and combined proton/photon beam radiation on pulmonary function in patients with resectable but medically inoperable non-small cell lung cancer.

STUDY OBJECTIVES: We evaluated the effects on pulmonary function of irradiating lung cancer with protons alone or protons combined with photons. DESIGN: Prospective phase I/II study. SETTING: University medical center. PATIENTS AND INTERVENTIONS: Ten patients with stage I-II non-small cell lung cancer (NSCLC) and FEV(1) < or = 1.0 L were irradiated with protons to areas of gross disease only, using 51 cobalt gray equivalents (CGE) in 10 fractions (protocol 1). Fifteen patients with stage I-IIIA NSCLC and FEV(1) > 1.0 L received 45-Gy photon irradiation to the primary lung tumor and the mediastinum, plus a 28.8-CGE proton boost to the gross tumor volume (protocol 2). MEASUREMENTS: Pulmonary function was evaluated prior to treatment and 1 month, 3 months, and 6 to 12 months following irradiation. RESULTS: In patients receiving protocol 1, no significant changes in pulmonary function occurred. In patients receiving protocol 2, at 6 to 12 months, the diffusion capacity of the lung for carbon monoxide had declined from 61% of predicted to 45% of predicted (p < 0.05), total lung capacity had declined from 114% of predicted to 95% of predicted (p < 0.05), and residual volume had declined from 160% of predicted to 132% of predicted (p < 0.05). Airway resistance increased from 3.8 to 5.2 cm H(2)O/L/s (p < 0.05). No statistically significant changes occurred in vital capacity, FEV(1), or PaO(2). CONCLUSIONS: Our observations indicate that it is feasible to apply higher-than-conventional doses of radiation at a higher-than-conventional dose per fraction without excess pulmonary toxicity when conformal radiation techniques with protons are used.

Aged↗

Research activities at the Loma Linda University and Proton Treatment Facility--an overview.

The Loma Linda University (LLU) Radiobiology Program coordinates basic research and proton beam service activities for the university and extramural communities. The current focus of the program is on the biological and physical properties of protons and the operation of radiobiology facilities for NASA-sponsored projects. The current accelerator, supporting facilities and operations are described along with a brief review of extramural research projects supported by the program. These include space craft electronic parts and shielding testing as well as tumorigenesis and animal behavior experiments. An overview of research projects currently underway at LLU is also described. These include: 1) acute responses of the C57Bl/6 mouse immune system, 2) modulation of gene expression in the nematode C. elegans and rat thyroid cells, 3) quantitation of dose tolerance in rat CNS microvasculature, 4) behavioral screening of whole body proton and iron ion-irradiated C57Bl/6 mice, and 5) investigation of the role of cell integration into epithelial structures on responses to radiation.

Animals↗

Normal tissue complication probability (NTCP) calculations as a means to compare proton and photon plans and evaluation of clinical appropriateness of calculated values.

Calculation of normal tissue complication probabilities (NTCP) for proton radiation therapy (PRT) and two photon radiation therapy techniques for cranial irradiation of childhood optic nerve gliomas was made. Evaluation of usefulness of calculated NTCP values for comparison of treatment plans and clinical appropriateness of computed data was used. Three radiation plans were calculated on datasets of children treated previously for optic nerve gliomas with PRT. Dose-volume histograms (DVH) were computed and used to calculate NTCP. Evaluated complication endpoints were necrosis, blindness, and cognitive impairment. Calculated NTCP depended strongly on tumor volume and the normal tissue volume exposed to high radiation doses. Dose conformity and steeper dose-gradient correlated with reduced NTCP. Regarding the chosen complication endpoints, PRT was superior to 3D photons; conventional photons were calculated to have the highest NTCPs. Differences might reach clinical significance for cognitive impairment, a frequently observed toxicity. Calculated NTCP values were highly dependent on implemented clinical data. Calculation of NTCP can be used for ranking of treatment plans and modalities. Highly dependent on implemented clinical data, the calculated percentage of NTCP might be more of a figure of merit than a real predictive value and requires comparison to clinical experience. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 351-358 (2000).

Child↗

Conformal proton radiation therapy of the posterior fossa: a study comparing protons with three-dimensional planned photons in limiting dose to auditory structures.

PURPOSE: Conventional radiation therapy for pediatric posterior fossa tumors can cause sequelae such as hearing loss and impairments in language and learning. Modern three-dimensional (3D) treatment techniques have improved dose conformity to the posterior fossa. This report compares the normal tissue dose-sparing capabilities of proton radiation therapy (PRT) with 3D conformal photon plans. METHODS AND MATERIALS: Nine children underwent previous PRT for primary CNS malignancies. Using original planning CT scans, the posterior fossa, inner and middle ear, and temporal lobes were delineated. Three-dimensional treatment plans were generated for protons and photons. Normal tissue exposures were calculated by averaging mean doses received and by analysis of dose-volume histogram. RESULTS: The 95% isodose encompassed the posterior fossa in all plans. Normal structures received markedly less radiation from PRT plans than from 3D photon plans. The cochlea received an average mean of 25 +/- 4% of the prescribed dose from PRT, and 75 +/- 6% from photons. Forty percent of temporal lobe volume was completely excluded using protons; with photons 90% of the temporal lobe received 31% of the dose. CONCLUSION: PRT resulted in increased dose sparing of normal structures analyzed. Posterior fossa conformity of 3D photons came at the expense of increasing amounts of normal tissue receiving low to moderate doses.

Child↗

Dose response of rat retinal microvessels to proton dose schedules used clinically: a pilot study.

PURPOSE: This preclinical rat pilot study quantifies retinal microvessel, endothelial, and pericyte population changes produced by proton irradiation METHODS AND MATERIALS: The left eyes of rats were irradiated with single doses of 8, 14, 20, and 28 Gy protons; right eyes, with two fractions. Animals were euthanized, and eyes were removed; elastase digests were prepared, and cell populations were counted in sample fields. Results were compared with unirradiated controls. RESULTS: Progressive time- and dose-dependent endothelial cell loss occurred following all schedules. Cell loss was significantly different from control values (p < 0.001) following 28 Gy and following 20 Gy (p < 0.05) in a single dose. Endothelial cell loss was the same for single- and split-dose schedules. Progressive endothelial cell loss produced vessel collapse and acellular vessel strands. Endothelial cells were in the G(0) phase of the mitotic cycle. 28 Gy produced photoreceptor cell loss. CONCLUSION: The retinal digest is an elegant bioassay to quantify the microvessel population response. Single- and split-dose schedules appear to yield similar outcomes, in terms of endothelial cell density.

Animals↗

Analysis of head motion prior to and during proton beam therapy.

PURPOSE: We report on the use of a noninvasive patient motion monitoring system to evaluate the amount of head motion prior to and during proton radiation therapy sessions. METHODS AND MATERIALS: Two optical displacement sensors, placed close to the patient's head, were used for online monitoring of the head position, with submillimeter accuracy. Motion data, including the difference between start and end position (Dx) and the maximum displacement during the recorded session (Dx-max), were acquired for pretreatment sessions to analyze alignment radiographs, and for treatment sessions. We have recorded 102 pretreatment and 99 treatment sessions in 16 patients immobilized with a thermoplastic mask, and 44 pretreatment and 56 treatment sessions in 13 patients immobilized with vacuum-assisted dental fixation. To avoid incorrect data analysis due to replicate observations, only 1 pretreatment and 1 treatment session per patient were selected at random for statistical comparison of mean or median motion parameters in different subgroups. RESULTS: Both techniques showed similar immobilization efficiencies. The median Dx and Dx-max values were 0. 18 mm and 0.46 mm, respectively, for 16 treatment sessions with mask immobilization, and 0.22 mm and 0.50 mm, respectively, for 13 treatment sessions with dental immobilization. Motion parameters for pretreatment and treatment sessions were not statistically different. CONCLUSION: Online verification of patient's head motion is feasible and provides valuable data for confirmation of proper treatment delivery in individual patients, as well as for the evaluation of different immobilization methods.

Adolescent↗

Value and perspectives of proton radiation therapy for limited stage prostate cancer.

BACKGROUND: This review article will focus on clinical results and limitations of proton beam irradiation. Possible technological, biological and medical perspectives will be addressed. PATIENTS AND METHODS: A total of 911 patients with limited stage prostate cancer were treated with proton beam irradiation at Loma Linda University between 1991 and 1996. Endpoints of this evaluation were biochemically no evidence of disease survival (bNED) as well as acute and late treatment-related toxicity. RESULTS: The bNED survival rate was 82% at 5 years. Among 870 patients evaluable for late toxicity the following late effects were observed: Grade 3/4: 0%, Grade 2 rectal: 3.5% and bladder: 5.4%. CONCLUSIONS: Despite relatively short follow-up times it seems justified to conclude that proton beam irradiation of prostate cancer can improve bNED rates by 10% and decrease Grade 2 late effects by more than 10%. There were no Grade 3 and 4 late effects.

Dose Fractionation, Radiation↗

Determination of the air w-value in proton beams using ionization chambers with gas flow capability.

The purpose of this work was to determine the w-value of air for protons using the paired gas method. Several plastic- and magnesium-walled chambers were used with air, synthetic air, nitrogen, and argon flowing gases. Using argon as a reference gas, the w-value of air was measured and ranged from 32.7 to 34.5 J/C for protons with energies encountered in radiotherapy. Using nitrogen as a reference gas, the w-value of air ranged from 35.2 to 35.4 J/C over the same range of proton energies. The w-value was found, at a given energy, to be independent of the ion chamber used. The uncertainty in these measurements was estimated at 5.2% at the 2sigma level. This uncertainty was dominated by the 4.4% uncertainty in the w-value of the reference gas.

Air↗

Acute effects of whole-body proton irradiation on the immune system of the mouse.

The acute effects of proton whole-body irradiation on the distribution and function of leukocyte populations in the spleen and blood were examined and compared to the effects of photons derived from a (60)Co gamma-ray source. Adult female C57BL/6 mice were exposed to a single dose (3 Gy at 0.4 Gy/min) of protons at spread-out Bragg peak (SOBP), protons at the distal entry (E) region, or gamma rays and killed humanely at six different times thereafter. Specific differences were noted in the results, thereby suggesting that the kinetics of the response may be variable. However, the lack of significant differences in most assays at most times suggests that the RBE for both entry and peak regions of the Bragg curve was essentially 1.0 under the conditions of this study. The greatest immunodepression was observed at 4 days postexposure. Flow cytometry and mitogenic stimulation analyses of the spleen and peripheral blood demonstrated that lymphocyte populations differ in radiosensitivity, with B (CD19(+)) cells being most sensitive, T (CD3(+)) cells being moderately sensitive, and natural killer (NK1.1(+)) cells being most resistant. B lymphocytes showed the most rapid recovery. Comparison of the T-lymphocyte subsets showed that CD4(+) T helper/inducer cells were more radiosensitive than the CD8(+) T cytotoxic/suppressor cells. These findings should have an impact on future studies designed to maximize protection of normal tissue during and after proton-radiation exposure.

Animals↗

Proton radiation therapy (PRT) for pediatric optic pathway gliomas: comparison with 3D planned conventional photons and a standard photon technique.

PURPOSE: Following adequate therapy, excellent long-term survival rates can be achieved for patients with optic pathway gliomas. Therefore, avoidance of treatment-related functional long-term sequelae is of utmost importance. Optimized sparing of normal tissue is of primary concern in the development of new treatment modalities. The present study compares proton radiation therapy (PRT) with a three-dimensional (3D)-planned multiport photon and a lateral beam photon technique for localized and extensive optic pathway tumors. METHODS AND MATERIALS: Between February 1992 and November 1997, seven children with optic pathway gliomas underwent PRT. For this study, we computed proton, 3D photon, and lateral photon plans based on the same CT data sets, and using the same treatment planning software for all plans. Radiation exposure for normal tissue and discrete organs at risk was quantified based on dose-volume histograms. RESULTS: Gross tumor volume (GTV) ranged from 3.9 cm3 to 127.2 cm3. Conformity index (relation of encompassing isodose to GTV volume) was 2.3 for protons, 2.9 for 3D photons, and 7.3 for lateral photons. The relative increase of normal tissue (NT) encompassed at several isodose levels in relation to NT encompassed by the 95% proton isodose volume was computed. Relative NT volume of proton plan isodoses at the 95%, 90%, 80%, 50%, and 25% isodose level increased from 1 to 1.6, 2.8, 6.4, to a maximum of 13.3. Relative volumes for 3D photons were 1.6, 2.4, 3.8, 11.5, and 34.8. Lateral plan relative values were 6, 8.3, 11.5, 19.2, and 26.8. Analysis for small (<20 cm3) and larger (> 80 cm3) tumors showed that protons encompassed the smallest volumes of NT at all isodose levels. Comparable conformity and high-dose gradient were achieved for proton and 3D photon plans in small tumors. However, with increasing tumor volume and complexity, differences became larger. At the 50% isodose level, 3D photons were superior to lateral photons for small tumors; this advantage was equalized for larger tumors. At the lowest isodose level, 3D photons encompassed the highest amount of NT. Analysis of organs at risk showed that PRT reduced doses to the contralateral optic nerve by 47% and 77% compared to 3D photons and lateral photons, respectively. Reductions were also seen for the chiasm (11% and 16%) and pituitary gland (13% and 16%), with differences at clinically relevant tolerance levels. Furthermore, reduced dose exposure of both temporal lobes (sparing 39% and 54%) and frontal lobes was achieved with PRT. CONCLUSION: PRT offered a high degree of conformity to target volumes and steep dose gradients, thus leading to substantial normal tissue sparing in high- and low-dose areas. It is expected that this will result in decreased long-term toxicity in the maturing child. Advantages of proton versus 3D photon plans became increasingly apparent with increasing target size and tumor complexity. Even in small tumors, conformity of 3D photon irradiation came at the expense of a larger amount of NT receiving moderate to low radiation doses. Lateral photons resulted in inferior dose distribution with high radiation exposure of clinically relevant normal tissues.

Child↗

Conformal proton therapy for early-stage prostate cancer.

OBJECTIVES: To assess the effect of proton radiation on clinical and biochemical outcomes for early prostate cancer. METHODS: Three hundred nineteen patients with T1-T2b prostate cancer and initial prostate-specific antigen (PSA) levels 15.0 ng/mL or less received conformal radiation doses of 74 to 75 cobalt gray equivalent with protons alone or combined with photons. No patient had pre- or post-treatment hormonal therapy until disease progression was documented. Patients were evaluated for biochemical disease-free survival, PSA nadir, and toxicity; the mean and median follow-up period was 43 months. RESULTS: Overall 5-year clinical and biochemical disease-free survival rates were 97% and 88%, respectively. Initial PSA level, stage, and post-treatment PSA nadir were independent prognostic variables for biochemical disease-free survival: a PSA nadir 0.5 ng/mL or less was associated with a 5-year biochemical disease-free survival rate of 98%, versus 88% and 42% for nadirs 0.51 to 1.0 and greater than 1.0 ng/mL, respectively. No severe treatment-related morbidity was seen. CONCLUSIONS: It appears that patients treated with conformal protons have 5-year biochemical disease-free survival rates comparable to those who undergo radical prostatectomy, and display no significant toxicity. A Phase III randomized dose-escalation trial is underway to define the optimum radiation dose for early-stage prostate cancer.

Follow-Up Studies↗

Proton dosimetry intercomparison based on the ICRU report 59 protocol.

BACKGROUND AND PURPOSE: A new protocol for calibration of proton beams was established by the ICRU in report 59 on proton dosimetry. In this paper we report the results of an international proton dosimetry intercomparison, which was held at Loma Linda University Medical Center. The goals of the intercomparison were, first, to estimate the level of consistency in absorbed dose delivered to patients if proton beams at various clinics were calibrated with the new ICRU protocol, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration factors. MATERIALS AND METHODS: Eleven institutions participated in the intercomparison. Measurements were performed in a polystyrene phantom at a depth of 10.27 cm water equivalent thickness in a 6-cm modulated proton beam with an accelerator energy of 155 MeV and an incident energy of approximately 135 MeV. Most participants used ionization chambers calibrated in terms of exposure or air kerma. Four ionization chambers had 60Co-based calibration in terms of absorbed dose-to-water. Two chambers were calibrated in a 60Co beam at the NIST both in terms of air kerma and absorbed dose-to-water to provide a comparison of ionization chambers with different calibrations. RESULTS: The intercomparison showed that use of the ICRU report 59 protocol would result in absorbed doses being delivered to patients at their participating institutions to within +/-0.9% (one standard deviation). The maximum difference between doses determined by the participants was found to be 2.9%. Differences between proton doses derived from the measurements with ionization chambers with N(K)-, or N(W) - calibration type depended on chamber type. CONCLUSIONS: Using ionization chambers with 60Co calibration factors traceable to standard laboratories and the ICRU report 59 protocol, a distribution of stated proton absorbed dose is achieved with a difference less than 3%. The ICRU protocol should be adopted for clinical proton beam calibration. A comparison of proton doses derived from measurements with different chambers indicates that the difference in results cannot be explained only by differences in 60Co calibration factors.

Algorithms↗

An automated technique for the simultaneous determination of cations in nanoliter volumes.

BACKGROUND: The study of ion transport along the renal tubule in vivo or in vitro requires a technique capable of analyzing ion concentrations in sample volumes of only a few nanoliters. This article describes a method for the analysis of cations at physiological concentrations in samples of tubular fluid taken from single renal tubules in vivo. Method. A background electrolyte composed of 2-[N-Morpholino] ethane-sulfonic acid (MES) (50 mmol/liter) and L-histidine (50 mmol/liter; pH congruent with 6.2), with the additives 18-crown-6 (1 mmol/liter) and methanol (30%) was used for the cation separation combined with conductivity detection. RESULTS: Capillary zone electrophoresis was used to separate NH4, K, Na, Ca, Li, Mg, and Ba in six minutes. Simultaneous quantitative analysis was performed for sodium and potassium, providing detection limits of 0.2 pmol for sodium and 30 fmol for potassium. The calibration plots were linear over three orders of magnitude, including the range of interest to clinical analysis. Data on the reproducibility and repeatability of peak areas and of the repeatability of migration times are reported. CONCLUSION: The results for sodium and potassium are in close agreement with those obtained by atomic absorption spectrometry, indicating that this is a suitable technique for the routine measurement of these cations in tubule fluid samples.

Automation↗