PubMed Health⌕ Search

Biomedical subjects

D P Spencer

Publications and source records attributed to D P Spencer.

17 recordsLinked to original sources
PubMed1999

Incorporation of functional status into dose-volume analysis.

The dose-volume histogram (DVH) has gained wide acceptance as a mechanism for reducing the voluminous data of a three-dimensional dose distribution into a two-dimensional graph. These graphs are often converted to a single figure of merit. This data reduction technique is used both for clinical treatment plan evaluation and as part of proposed systems for estimating control and complication probabilities. It has long been recognized that a major shortcoming of the DVH as an analysis tool is that all spatial information is discarded. A subtler problem, which is addressed in this work, is that the DVH also implies homogeneity of biological consequence of irradiation in what may be a functionally heterogeneous volume of tissue. An extension to the DVH, the functional dose-volume histogram, or dose-function histogram (DFH), is proposed, that explicitly includes quantitative three-dimensional functional information. The concept is illustrated by the use of SPECT imaging to assess the functional status of irradiated lung.

Humans↗
PubMed1998

Serial in vivo observations of cerebral vasculature after treatment with a large single fraction of radiation.

To test whether single high doses of radiation, similar to those used with radiosurgery, given to normal cerebral vasculature can cause changes in leukocyte-vessel wall interactions and tissue perfusion, a rat pial window model was used to view the cerebral vasculature, facilitating repeated in vivo observations of microcirculatory function. An attachment for a 4 MV linear accelerator was designed to deliver a well-collimated 2.2-mm beam of radiation to a selected region of rat brain. Sequential measurements of leukocyte-endothelial cell interactions, relative change in blood flow with laser Doppler flowmetry and vessel length density were performed prior to and at 24 h and 3 weeks after treatment with 15, 22.5 or 30 Gy, given in a single fraction. Significant increases in leukocyte-endothelial cell interactions were seen 24 h and 3 weeks after irradiation that were dependent on dose, particularly in arteries. Changes were apparent in both arteries and veins at 24 h, but by 3 weeks the effects in arteries predominated. Decreases in vessel length density and blood flow were observed and became greater with time after treatment. A variety of morphological changes were observed in irradiated arteries, including formation of aneurysmal structures, endothelial denudation and thrombus formation. These results suggest that: (1) An increase in leukocyte-vessel wall interactions occurs after irradiation; (2) cerebral arterioles are more sensitive than veins to radiation administered in this fashion; and (3) the increase in leukocyte-vessel wall interactions likely contributes to reduction of or loss of arteriolar flow, with resultant loss of flow to dependent microvascular vessels.

Animals↗
PubMed1997

Quantification of radiation-induced regional lung injury with perfusion imaging.

PURPOSE: To better understand the dose and time dependence of radiation therapy (RT)-induced regional lung dysfunction as assessed by changes in regional lung perfusion. METHODS AND MATERIALS: Patients who were to receive RT for tumors in and around the thorax, wherein portions of healthy lung would be incidentally irradiated, were prospectively studied. Regional function was assessed pre- and post-RT with single photon emission computed tomography (SPECT) lung perfusion scans, obtained following the intravenous administration of approximately 4 mCi of technetium-99m macroaggregated albumin. Pre-RT computed tomography (CT) scans were used to calculate the three-dimensional (3D) dose distribution, reflecting tissue density inhomogeneity corrections. Each SPECT scan was correlated with the pre-RT CT scan, and the 3D dose distribution. Changes in regional lung perfusion were correlated with regional RT dose, at various time intervals following radiation. RESULTS: The data from 20 patients (7 breast cancer, 5 lymphoma, 1 esophagus, 1 sarcoma, and 6 lung cancer) have been analyzed. Patients with gross intrathoracic lung cancers causing obstruction of regional pulmonary arteries were not included. For most patients, there is a statistically significant dose-dependent reduction in regional blood flow at all time points following radiation. While a time dependence is suggested in the high dose range, the limited amount of data prevents meaningful statistical evaluation. CONCLUSIONS: Radiation therapy-induced regional lung dysfunction occurs in a dose-dependent manner and develops within 3-6 months following radiation. In contrast to classical "sigmoid" dose-response curves, described mainly for changes following whole lung irradiation, these data suggest a more gradual relationship between regional dysfunction and RT dose. Retraction of irradiated lung with secondary movement of unirradiated lung into the "3D-defined irradiated volume" may have introduced inaccuracies into this analysis. Additional studies are currently underway to assess this possibility and better refine this dose-response curve. Studies are underway to determine if changes in assessments of whole lung function, such as pulmonary function tests, can be predicted by summing the regional changes observed.

Dose-Response Relationship, Radiation↗
PubMed1995

Conformal radiation therapy with fixed shaped coplanar or noncoplanar radiation beam bouquets: a possible alternative to radiosurgery.

PURPOSE: Three-dimensional (3D) geometric conformation of the therapeutic dose volume to the shape of a target tissue volume is the motivation for both conformal radiotherapy and radiosurgery. Although noncoplanar arcs have a clear physical and geometric advantage over fixed fields for small spherical targets, those advantages are reduced for large or irregularly shaped targets where static fields can be individually shaped. We have developed a system that allows efficient and flexible design and reliable delivery of customized "bouquets" of fixed nonopposed coplanar or noncoplanar shaped fields, resulting in highly uniform dose distributions. This report describes our initial experience using beam bouquets to treat intracranial lesions. METHODS AND MATERIALS: Patients with primary (11) or metastatic (4) intracranial lesions with a maximum diameter less than approximately 6 cm, most of whom candidates for single-fraction radiosurgery, were treated with beam bouquets of four to eight nonopposed coplanar or noncoplanar beams. Doses ranged from 16-20 Gy in four fractions for recurrent lesions (8) to 45 to 68 Gy in 25 to 34 fractions for primary lesions (7). The patients were immobilized with custom foam head supports and face masks attached to a fixed base plate. Planning computed tomography scans were acquired, from which the physician developed the custom beam bouquet using 3D treatment-planning tools. The bouquet was designed based primarily on geometric concerns. The bouquet was subsequently modified to add wedge filters chosen by vector analysis of dose gradients to achieve uniform dose over the volume of beam crossfire. At the time of treatment, the isocenter was placed using the instructions provided by the treatment-planning system and pretreatment orthogonal port films were compared to digitally reconstructed radiographs (DRR) to assure proper isocenter placement. For several situations, the 3D dose distributions resulting from alternative coplanar and noncoplanar plans were compared. RESULTS: Each patient was treated without incident. Daily pretreatment port films showed excellent reproducibility of isocenter placement in 87% of setups. With short follow-up (0-12 months), two patients with recurrent glioblastoma experienced clinical deterioration 2 to 4 weeks following treatment. One had increased edema on scans and responded to steroids. Six patients clinically improved following radiation therapy. Review of alternative treatment plans reveals that the relative utility of coplanar vs. noncoplanar beams is likely dependent on the location of the lesion. Noncoplanar beam bouquets are likely preferable to coplanar beams when the target is located in the central regions of the head. Coplanar beams are likely adequate, and possibly preferable, for peripherally located targets. CONCLUSION: The biological advantages of fractionation and the physical advantages of radiosurgery are exploited with this approach. The use of multiple nonopposed coplanar or noncoplanar conformal wedged fields provides a uniform dose to the target and acceptable dose gradient at the target edge. This technique may prove to be an alternative to arc-based radiosurgery in some settings and has the potential advantages that fractionation should improve the therapeutic ratio, and each beam can be individually shaped to conform to irregularly shaped targets. Additional studies are underway to improve this system and better define its utility.

Adult↗
PubMed1995

Inhibition of radiation-induced up-regulation of leukocyte adhesion to endothelial cells with the platelet-activating factor inhibitor, BN52021.

PURPOSE: The inflammatory process is likely involved in normal tissue damage after radiation exposure, yet few studies have directly evaluated the factors that might be involved in the regulation of inflammation after irradiation in vivo. We tested the hypothesis that platelet-activating factor, a neutrophil agonist synthesized by endothelial cells, is involved in the upregulation of radiation-induced leukocyte-endothelial cell interactions by using an inhibitor of its receptor, BN52021. METHODS AND MATERIALS: Fischer-344 rats with dorsal skin-fold window chambers were randomized to three experimental groups: control (sham irradiation); 6 Gy radiation; and 6 Gy + BN52021. BN52021 (0.5 mg/kg) was administered 5 min prior to 6 Gy radiation. Leukocytes were stained in vivo with i.v. acridine orange for visualization with fluorescent microscopy. Venous vessel diameters were measured and number of rolling leukocytes were counted per 30-s period. The number of adhering leukocytes per unit surface area was also determined. Differences among the three experimental groups for rolling and adhering leukocytes were analyzed using a mixed-effects linear model with vessel shear rate used as a covariate. Results are reported as means +/- standard errors. RESULTS: Irradiation caused upregulation of leukocyte rolling, as compared with sham-treated controls (p = 0.04): the BN compound in addition to radiation did not downregulate this effect. Irradiation also upregulated leukocyte adhesion (p < 0.001), but the addition of BN52021 prior to irradiation blocked this effect. The drug did not affect heart rate or blood pressure. CONCLUSIONS: These results support the hypothesis that radiation-induced upregulation of leukocyte adhesion is mediated by platelet-activating factor. These results are consistent with prior reports that platelet-activating factor is not involved in leukocyte rolling, which involves separate families of adhesion molecules from those that regulate adhesion. BN52021, a ginkolide, or other related drugs might provide a useful pharmacological means to prevent or ameliorate inflammatory pathways that are invoked after radiation exposure.

Animals↗
PubMed1995

The role of three dimensional functional lung imaging in radiation treatment planning: the functional dose-volume histogram.

PURPOSE: During thoracic irradiation (XRT), treatment fields are usually designed to minimize the volume of nontumor-containing lung included. Generally, functional heterogeneities within the lung are not considered. The three dimensional (3D) functional information provided by single photon emission computed tomography (SPECT) lung perfusion scans might be useful in designing beams that minimize incidental irradiation of functioning lung tissue. We herein review the pretreatment SPECT scans in 86 patients (56 with lung cancer) to determine which are likely to benefit from this technology. METHODS AND MATERIALS: Prior to thoracic XRT, SPECT lung perfusion scans were obtained following the intravenous injection of approximately 4 mCi of 99mcTc-labeled macro-aggregated albumin. The presence of areas of decreased perfusion, their location relative to the tumor, and the potential clinical usefulness of their recognition, were scored. Patients were grouped and compared (two-tailed chi-square) based on clinical factors. Conventional dose-volume histograms (DVHs) (DVFHs) are calculated based on the dose distribution throughout the computed tomography (CT)-defined lung and SPECT-defined perfused lung, respectively. RESULTS: Among 56 lung cancer patients, decreases in perfusion were observed at the tumor, adjacent to the tumor, and separate from the tumor in 94%, 74%, and 42% of patients, respectively. Perfusion defects adjacent to the tumor were often large with centrally placed tumors. Hypoperfusion in regions separate from the tumor were statistically most common in patients with relatively poor pulmonary function and chronic obstructive pulmonary disease (COPD). Considering all SPECT defects adjacent to and separate from the tumor, corresponding CT abnormalities were seen in only approximately 50% and 20% of patients, respectively, and were generally not as impressive. Following XRT, hypoperfusion at and separate from the tumor persisted, while defects adjacent to the tumor improved in several patients. In four patients who achieved a complete response scored by CT with chemotherapy prior to XRT, persistent hypoperfusion was present at and adjacent to the tumor site in three. Among 30 patients with cancers not arising in the lung (14 breast, 12 lymphoma, 4 others), perfusion defects were seen in only 4 (2 adjacent and 2 apart). Recognition of decreases in perfusion mainly impacted on treatment planning for a few patients with poor pulmonary function and limited target volumes. DVFHs have been useful in beam selection for patients with marked perfusion heterogeneities. CONCLUSIONS: Lung perfusion scans provide functional information not provided by CT scans that can be useful in designing radiation treatment beams that minimize incidental irradiation of the function regions of the lung. This approach appears to be most helpful in patients with gross intrathoracic lung cancer, especially those with small targets and relatively poor pulmonary function. One limitation of this approach is that some of the defects adjacent to the tumor site reperfuse following treatment, indicating that these scans identify perfusion rather than potential perfusion. Three dimensional functional data can be used to generate DVFHs that may be more predictive of the physiological consequences of the radiation than conventional DVHs. Additional work is currently underway to test this hypothesis.

Forced Expiratory Volume↗
PubMed1995

A customized head and neck support system.

PURPOSE: To describe a customized head and neck immobilization system for patients receiving radiotherapy including a head support that conforms to the posterior contour of the head and neck. METHODS: The system includes a customized headrest to support the posterior head and neck. This is fixed to a thermoplastic face mask that molds to the anterior head/face contours. The shape of these customized head and neck supports were compared to "standard" supports. RESULTS: This system is comfortable for the patients and appears to be effective in reproducing the setup of the treatment. CONCLUSIONS: The variability in the size and shape of the customized posterior supports exceeded that of "standard" headrests. It is our clinical impression that the customized supports improve reproducibility and are now a standard part of our immobilization system. The quantitative analysis of the customized headrests and some commonly used "standard" headrests suggests that the customized supports are better able to address variabilities in patient shape.

Equipment Design↗
PubMed1995

The effectiveness of immobilization during prostate irradiation.

PURPOSE: To evaluate the effect of a hemibody foam cradle on the reproducibility of patient setup during external beam radiation treatment of prostate cancer. METHODS AND MATERIALS: Between January 1992 and April 1993, 74 patients received external beam radiation treatment to the prostate +/- nodes, generally with a four-field box technique. Forty-four of the 74 patients had a custom-made hemibody foam cast used in an attempt to improve setup accuracy. A review of the routine weekly port films was performed following the completion of therapy to determine the reproducibility of patient setup in all 74 patients. The physician's request of an isocenter shift was used as an indicator of reproducibility. Neither the treating technologists nor the physicians knew at the time the films were taken that the port films would be reviewed for setup reproducibility at a later date. The results were compared between the patients treated with (44) and without (30) an immobilization device. RESULTS: In the 44 immobilized patients, 213 routine checks of the isocenter were performed during the 7-week course of radiation therapy. In 17.4% of these instances (37 out of 213), an isocenter shift was requested. This rate is compared to 23.1% (30 out of 130) in the 30 patients who did not have the immobilization device (p < 0.2). There was a statistically significant reduction in isocenter shifts requested in the anterior to posterior direction in the patients who were immobilized, 5.1% (9 out of 175) vs. 12.6% (13 out of 103) (p < 0.05, two tailed chi-square test). There was no significant improvement in the reproducibility of isocenter placement in the cephalad to caudal or right to left directions. CONCLUSIONS: This custom-made hemibody foam cradle appears to improve the reproducibility of patient setup during the 7-week course of fractionated external beam irradiation for patients with adenocarcinoma of the prostate. This type of immobilization device is now routinely used in our clinic and is recommended for all patients receiving pelvic radiotherapy. These devices are likely to be particularly useful when contemplating dose escalation to minimize the volume of bladder and rectum included in the treatment fields.

Adenocarcinoma↗
PubMed1994

To treat or not to treat the internal mammary nodes: a possible compromise.

PURPOSE: A method for designing partly wide tangential fields that irradiate the superiorly placed internal mammary nodes, yet exclude the inferiorly placed internal mammary nodes and the cardiac tissue, is described for patients receiving tangential radiation for breast cancer. METHODS AND MATERIALS: Patients are immobilized in hemibody foam cradles. A CT study is performed with a series of fiducial markers. The CT data set can then either be transferred to the three-dimensional treatment planning computer for sophisticated treatment planning, or can be viewed to design partly wide tangential fields "by hand." This latter method is far less time consuming and, we believe, usually adequate, given the uncertainties in identifying the location of the internal mammary nodes. RESULTS: This technique has been implemented in our clinic and has been used to treat approximately 15 patients. In four of these patients, a formal dose-volume histogram analysis revealed that these partly wide tangential fields can adequately exclude the cardiac volume and include the superiorly placed internal mammary nodes. Modest reductions in the pulmonary volume that is incidentally irradiated are seen compared to conventional wide tangents that irradiate the entire length of the internal mammary chain. CONCLUSION: While controversy remains regarding the appropriateness of internal mammary nodal irradiation for patients with breast cancer, the technique described represents an attractive compromise. Selective irradiation of the superiorly placed internal mammary nodes (which are those at greatest risk for involvement) with customized "partly wide" tangential fields is possible. This treatment technique may provide the survival advantage that might be seen with internal mammary node irradiation, yet avoid the possible cardiac morbidity.

Breast Neoplasms↗
PubMed1993

The utility of SPECT lung perfusion scans in minimizing and assessing the physiologic consequences of thoracic irradiation.

PURPOSE: Three-dimensional single photon emission computed tomography lung perfusion scans (SPECT) provide a unique quantitative 3-dimensional map of the distribution of functioning pulmonary vascular/alveolar subunits, information not provided by other imaging modalities. This report describes our initial experience utilizing these scans to assist in the design of radiation treatment beams and to assess changes in regional lung function following irradiation. METHODS AND MATERIALS: Patients were immobilized and scanned in the treatment position with appropriate fiducial markers. Four millicuries of technetium 99M microaggregated albumin were injected and SPECT images of the lung were generated. Pre-treatment SPECT images were used to help design radiation beams to minimize irradiation of functioning lung. Pre- and post-treatment scans were compared to assess changes in regional function. These changes in function were then correlated with the regional radiation dose. RESULTS: Pre-radiotherapy SPECT scans were obtained in 18 patients (11 with lung cancer). Marked variations in regional function were frequently noted. In patients with primary lung tumors, these variations were not necessarily immediately adjacent to the tumor volume. In general, patients with poor pulmonary function pre-treatment, in whom one would like to spare as much normal lung as possible, had the most non-uniform distribution throughout the lung of functioning vascular/alveolar subunits. In these cases, pre-treatment scans were most useful in designing radiation portals to minimize irradiation of functioning lung. SPECT scans were also used to detect changes in regional lung function secondary to radiotherapy in four patients. With doses in excess of 40 Gy, reductions in regional function were noted 1-6 months following completion of radiotherapy. These reductions were not necessarily accompanied by reductions in conventional pulmonary function tests, which are assessments of whole lung function and may not reflect regional lung injury if the volume affected is small. CONCLUSIONS: SPECT lung scans provide an excellent means of assessing regional lung function, superior to that obtainable with planar images. The functional data provided by the SPECT images is useful in designing "optimal" radiation treatment beams and in assessing the effect of radiotherapy on regional lung functions. Efforts are continuing in our laboratory to develop a dose response curve for regional lung damage using the tools of SPECT scanning and 3-dimensional dose calculations.

Aged↗
PubMed1993

3-dimensional optimization of multiple arcs for stereotactic radiosurgery.

PURPOSE: During linear accelerator-based radiosurgery, the physicians and physicists need to determine which combination of treatment arcs are "best" with regard to target coverage and incidental dose to adjacent structures. This is a complex problem, especially when targets are geometrically close to critical structures. The purpose of this article is to present a method to mathematically determine a set of arcs to produce desired target and normal structure dose distributions in linear accelerator radiosurgery. METHODS AND MATERIALS: Nonlinear least squares regression was used to determine the table angles and gantry angle arc ranges and their associated beam weights appropriate to linear accelerator radiosurgery. RESULTS: Three cases are presented: (a) critical structure close to target volume; (b) target volume too large for the largest collimator to cover the volume with one isocenter and a standard plan; (c) target volume located within one critical structure and close to another critical structure. The optimized treatment plans are all shown to be superior to a defined standard plan. CONCLUSION: The method successfully enables one to determine nonstandard arcs which achieve the desired results. In particular, the method enables one to find clinical treatment solutions, even when the desired results cannot be a priori defined.

Humans↗
PubMed1993

Craniospinal irradiation for trilateral retinoblastoma following ocular irradiation.

A case study is presented. Craniospinal radiotherapy and a three-fold pineal boost for trilateral retinoblastoma were delivered to a patient previously irradiated for ocular retinoblastoma. The availability of CT-based three-dimensional treatment planning provided the capability of identifying the previously irradiated volume as a three-dimensional anatomic structure and of designing a highly customized set of treatment beams that minimized reirradiation of that volume.

Brain Neoplasms↗
PubMed1991

Measurement of bioreduction rates of cells with distinct responses to ionizing radiation and cisplatin.

A low frequency electron paramagnetic resonance (EPR) spectrometer has been used to measure the bioreduction rate of an exogenously added nitroxide free radical species. Measurements have been made in a well controlled, in vitro system using an X-ray and cisplatin sensitive Chinese hamster ovary (CHO) cell line, xrs-5, and partial revertants which display wild-type levels of sensitivity to X-rays but retain xrs-5 levels of cisplatin sensitivity. The xrs-5 cells reduce this radical species at a rate which is approx. 50% that of the wild-type CHO cell line, K1. The partial revertants maintain this defect in bioreduction despite their decrease in radiosensitivity. However, the bioreduction rate observed in these cells correlates with their sensitivity to the chemotherapeutic drug cisplatin. Low frequency EPR allows measurements and imaging of living tissue and may be of value as a predictive assay of human tumor response to chemotherapy.

Animals↗
PubMed1991

The influence of volume on the tolerance of the brain to radiosurgery.

Radiosurgery (delivery of a high dose of radiation to a small volume of the brain) is usually well tolerated since the volume of brain irradiated is small. Despite growing interest in radiosurgery, the influence of the volume of brain irradiated on the tolerance of the brain to radiation is not well understood. The results of six studies reporting clinically significant radiation reactions following radiosurgery for arteriovenous malformations are reviewed. In the combined series, 23 (9%) of 255 patients developed a clinically significant radiation reaction. The volume of brain irradiated and the dose delivered in each of these 23 patients are presented. The compiled data suggest that the previously presented guidelines may underestimate the risks of radiosurgery. Additional clinical and experimental data are needed to determine "safe" doses of radiation to be used during radiosurgery.

Brain↗
PubMed1988

Direct measurement of nitroxide pharmacokinetics in isolated hearts situated in a low-frequency electron spin resonance spectrometer: implications for spin trapping and in vivo oxymetry.

The pharmacokinetics of two nitroxides were investigated in isolated rat hearts situated in a low-frequency electron spin resonance spectrometer. The spin labels 2,2,3,3,5,5-hexamethyl-1-pyrrolidinyloxy and 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy were chosen for their physiochemical analogy to the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and its corresponding spin-trapped adduct, 2-hydroxy-5,5-dimethyl-1-pyrrolidinyloxy (DMPO-OH). The bioreductive rates of the two nitroxides were measured during constant perfusion as well as during ischemia and are discussed in terms of a two-compartment pharmacokinetic model. These data provide information necessary to the design and application of spin traps to detect oxy radicals during reperfusion of ischemic tissue and suggest the feasibility of monitoring free-radical processes in intact, functioning mammalian tissues by using a low-frequency electron spin resonance spectrometer.

Animals↗
PubMedDate not supplied

Encapsulated liquid crystals as probes for remote thermometry.

A temperature probe based on the magnetic resonance properties of an encapsulated liquid crystal has been investigated. Large changes in magnetic resonance signals occur as the liquid crystal undergoes a phase transition from an anisotropic (nematic) state to the isotropic liquid. The low latent heat of such phase transitions allows for rapid phase changes during a hyperthermia treatment. Transition temperatures can be tailored by adding suitable compounds such as analogues of the liquid crystal or various solvents. Encapsulation is required to maintain the integrity of the liquid crystal, particularly for applications in vivo. Results of preliminary studies designed to demonstrate the technical feasibility of the concept are presented.

Benzylidene Compounds↗