Highly efficient and sensitive patient-specific quality assurance for spot-scanned proton therapy.

The purpose of this work was to develop an end-to-end patient-specific quality assurance (QA) technique for spot-scanned proton therapy that is more sensitive and efficient than traditional approaches. The patient-specific methodology relies on independently verifying the accuracy of the delivered proton fluence and the dose calculation in the heterogeneous patient volume. A Monte Carlo dose calculation engine, which was developed in-house, recalculates a planned dose distribution on the patient CT data set to verify the dose distribution represented by the treatment planning system. The plan is then delivered in a pre-treatment setting and logs of spot position and dose monitors, which are integrated into the treatment nozzle, are recorded. A computational routine compares the delivery log to the DICOM spot map used by the Monte Carlo calculation to ensure that the delivered parameters at the machine match the calculated plan. Measurements of dose planes using independent detector arrays, which historically are the standard approach to patient-specific QA, are not performed for every patient. The nozzle-integrated detectors are rigorously validated using independent detectors in regular QA intervals. The measured data are compared to the expected delivery patterns. The dose monitor reading deviations are reported in a histogram, while the spot position discrepancies are plotted vs. spot number to facilitate independent analysis of both random and systematic deviations. Action thresholds are linked to accuracy of the commissioned delivery system. Even when plan delivery is acceptable, the Monte Carlo second check system has identified dose calculation issues which would not have been illuminated using traditional, phantom-based measurement techniques. The efficiency and sensitivity of our patient-specific QA program has been improved by implementing a procedure which independently verifies patient dose calculation accuracy and plan delivery fidelity. Such an approach to QA requires holistic integration and maintenance of patient-specific and patient-independent QA.

Utilizing an electronic portal imaging device to monitor light and radiation field congruence.

A method to investigate light and radiation field congruence utilizing a commercially available amorphous silicon electronic portal imaging device (EPID) was developed. This method employed an EPID, the associated EPI software, and a diamond-shaped template. The template was constructed from a block tray in which Sn/Pb wires, 1 mm in diameter, were embedded into a diamond shaped groove milled into the tray. The collimator jaws of the linac were aligned such that the light field fell directly on the corners of the diamond. A radiation detection algorithm within the EPI software determined the extent of the radiation field. The light and radiation field congruence was evaluated by comparing the vertexes of the diamond reference structure to the detected radiation field. In addition, the digital jaw settings were recorded and later compared to the light field detected on the films and EPIs. Three linear accelerators were tracked for a period ranging from 2-8 months. Light radiation field congruence tests with films and EPIs were comparable, yielding a difference of less than 0.6 mm, well within the allowed 2-mm tolerance. A disparity was observed in the magnitude of the detected light field. The X and Y dimensions of the light field measured with film differed by less than or equal to 1.4 mm from the digital collimator settings, whereas the values extracted from the EPIs differed by up to 2.5 mm. Based on these findings, EPIs were found to be a quick and reliable alternative to film for qualitative and relative analyses.

Radiation-induced changes in gene expression and distribution of atrial natriuretic peptide (ANP) in different anatomical regions of the rat heart.

PURPOSE: To examine the effects of whole-heart irradiation on gene expression and distribution of atrial natriuretic peptide (ANP) in atrial appendages and left ventricles of the rat heart. MATERIAL AND METHODS: Female Sprague-Dawley rats were irradiated with a single dose of 0, 15 or 20 Gy locally to the heart. At intervals up to 16 months post-irradiation, the localization of ANP was examined using immunohistochemical techniques. Absolute mRNA concentrations were determined using the competitive PCR assay. RESULTS: Histological and immunohistochemical studies demonstrated that whole-heart irradiation caused a reduction of atrial ANP, which is due to a substantial loss of ANP-producing atrial myocytes and accumulation of collagen (replacement fibrosis). On the other hand, ANP became detectable in the subendocardium of the irradiated left ventricles. Positive staining of ANP was mainly found in the proximity of injured areas consisting of degeneration of myocytes and fibrosis. At the transcriptional level, reduction of atrial ANP expression at 1 month post-irradiation was followed by recovery at 3 months. Thereafter, ANP mRNA concentrations followed the mRNA pattern of controls and even appeared to increase at 16 months. In the left ventricle, dose-dependent and progressive elevation of ANP gene expression could be observed during the observation period and reached a 20-fold increase as compared with sham-irradiated age-matched controls. CONCLUSIONS: The distribution of ANP after local irradiation of the rat heart depends on the severity of the pathological/structural changes (i.e. myocyte degeneration and fibrosis). In radiation-induced heart disease, elevated ANP expression in the left ventricle is most probably involved in the observed chronic elevation of plasma ANP levels.

Surgical anatomy of the C-2 pedicle.

OBJECT: The goal of this anatomical study was to investigate the surgical and radiographic anatomy of the C-2 pedicle in relation to transpedicular screw placement in occipitocervical stabilization and to establish anatomical guidelines for the placement of C-2 pedicle screws. METHODS: The C-2 pedicles in 10 cadaveric spines were evaluated using both computerized tomography (CT) scanning and manual measurements. The specimens were scanned; the mediolateral and rostrocaudal angulations of each pedicle were measured, with the midline sagittal plane and the inferior endplate of the C-2 facet, respectively, as references, and values were recorded in 1 degrees increments by using a digital goniometer. The height, width, and length of the pedicles were also measured on the CT scans. Based on these measurements in conjunction with direct visualization of the C-2 pedicle through the C 1-2 interlaminar space pedicle screws were then placed. The distances from the screw entry point to the midline, C2-3 joint line, and the medial aspect of the vertebral artery were also measured. Repeated CT scanning was then performed to assess screw placement. The average pedicle height, width, and length measured 9.1 mm, 7.9 mm, and 16.6 mm, respectively, and the medial, inclination and rostrocaudal angulation averaged 35.2 degrees and 38.8 degrees, respectively. The cortex of the pedicle was not violated in any of the 20 cadaveric specimens. CONCLUSIONS: Adequate preoperative imaging studies in conjunction with direct visualization of the C-2 pedicle make transpedicular fixation safe and effective.

Structural changes in the auricles of the rat heart after local ionizing irradiation.

BACKGROUND AND PURPOSE: Irradiation of the heart may lead to late cardiovascular complications and depending on the dose to cardiac-related death. There is increasing evidence that left atrial appendages play an important role in left ventricular filling especially in cardiac disease. The aim of the present study was to investigate the radiation response of the atria of the rat heart (auricles in particular) at morphological, histological and transcriptional level. MATERIAL AND METHODS: Sprague-Dawley rats were irradiated with a single dose locally on the heart (0-22.5 Gy). End-diastolic diameters of left auricles were measured during evaluation of cardiac function. Histopathological evaluations were performed at various time points up to 16 months post irradiation. Changes in mRNA expression of procollagen types I and III and pro-fibrogenic cytokines (TGF-beta1 and IL-1beta) were investigated using competitive PCR. RESULTS: Irradiation leads to a dose-dependent decrease in end-diastolic diameter of the left auricles. This decrease was observed at 4 months post-irradiation, where no gross damage of the ventricle has been reported. Histologically, epicardial fibrosis was found already 1 month post irradiation, and the frequency/severity of the structural changes appeared to be dose-dependent and progressive with time post irradiation. At 9 months, fibrosis was observed in all three layers (epicardium, myocardium and endocardium) of both auricles. On the level of gene expression, increases in procollagen types I and III were observed at 12 and 3 months post irradiation, respectively. Increases in IL-1beta and TGF-beta1, cytokines known to influence collagen deposition at different levels, preceded the upregulation of procollagen mRNA. CONCLUSIONS: Auricles of the rat heart show a marked pathological response to ionizing radiation, characterized by generalized accumulation of collagen (fibrosis) and a reduction of end-diastolic diameter. The reduction of auricular volume and loss of elasticity will negatively contribute to the pump function of the irradiated ventricle.

Ossification of the ligamentum flavum as a cause of myelopathy in North America: report of three cases.

Myelopathy caused by ossification of the ligamentum flavum is a rare condition in North America. The authors describe three patients whose myelopathy was attributed to posterior cord compression warranting laminectomy to decompress the cervical spine (in one patient) and the thoracic spine (in two patients). The spinal computed tomographic scan (especially after myelography) can be instrumental in guiding the management of this condition.

Guide to clinical use of electronic portal imaging.

The Electronic Portal Imaging Device (EPID) provides localization quality images and computer-aided analysis, which should in principal, replace portal film imaging. Modern EPIDs deliver superior image quality and an array of analysis tools that improve clinical decision making. It has been demonstrated that the EPID can be a powerful tool in the reduction of treatment setup errors and the quality assurance and verification of complex treatments. However, in many radiation therapy clinics EPID technology is not in routine clinical use. This low utilization suggests that the capability and potential of the technology alone do not guarantee its full adoption. This paper addresses basic considerations required to facilitate clinical implementation of the EPID technology and gives specific examples of successful implementations.

Changes in transforming growth factor-beta (TGF-beta 1), procollagen types I and II mRNA in the rat heart after irradiation.

PURPOSE: To study alteration in gene transcription (transforming growth factor-beta 1 and procollagen types I and III) involved in radiation-induced cardiac damage. MATERIALS AND METHODS: Female Sprague-Dawley rats were irradiated with a single dose of 0, 15, 20 or 25 Gy locally on the heart. At intervals up to 16 months after irradiation, absolute amounts of mRNA were quantified using a (semi-nested) competitive PCR assay. All values were normalized to equal input cDNA with respect to their GAPDH content. RESULTS: After irradiation, left ventricular TGF-beta 1 mRNA levels increased sharply. This response was bi-phasic with peaks at days 1 and 12 (maximum 6-fold baseline), then returning to control levels by 1 month. After 20 Gy, a persistent elevation was observed from 6 months, but this elevation was less profound (approximately 1.5-fold baseline) when compared with the early response (1-12 days). Absolute mRNA levels of procollagen type I hardly changed during the first 6 months, but thereafter these levels increased progressively until the end of observation. An age-related increase in procollagen I was also observed. Procollagen type III mRNA levels were increased between days 1 and 12, returned to control values and remained low up to 6 months, then mRNA levels rose again with increasing time post-treatment. CONCLUSION: The difference in time-course between TGF-beta 1 and procollagen mRNA expression after local heart irradiation and ageing strongly suggest that the late up-regulation of both procollagen types in the left ventricle occurs without TGF-beta 1 over-expression.

Detection and quantitative measurement of transforming growth factor-beta1 (TGF-beta1) gene expression using a semi-nested competitive PCR assay.

A polymerase chain reaction (PCR) technique was optimized for detection and quantification of very low concentrations (down to a few molecules) of transforming growth factor beta1 (TGF-beta1) mRNA. The strategy involved a combination of a competitive PCR assay and a semi-nested PCR. In the present study, the semi-nested PCR technique was tested in several rat organs containing different concentrations of target mRNA. A control fragment for TGF-beta1 was used to correct for differences in amplification of various cDNA samples. TGF-beta1 mRNA levels were also corrected according to the abundance of the "housekeeping" gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in the same samples. The differences of sensitivity among the standard (one-step) and semi-nested (two-step) competitive PCR assays for the detection of TGF-beta1 are discussed. In conclusion, the semi-nested PCR protocol provides greatly enhanced sensitivity over standard PCR analysis. It is a reproducible and very specific method for quantification of only a few molecules of TGF-beta1 mRNA in a background of non-target molecules.

Skull-base trauma: neurosurgical perspective.

Trauma to the cranial base can complicate craniofacial injuries and lead to significant neurological morbidity, related to brain and/or cranial nerve injury. The optimal management involves a multidisciplinary effort. This article provides the neurosurgeon's perspective in management of such trauma using a 5-year retrospective analysis of patients sustaining skull-base trauma. The salient features of anterior and middle skull-base (temporal bone) trauma are summarized, and the importance of frontal basilar trauma as well as brain injury is evident. With these injuries, all cranial nerves (except 9 to 12) are at risk; the olfactory nerve and the facial nerve are the first and second, respectively, to sustain injuries. This retrospective analysis provides a better understanding of cranial base trauma and its management. It emphasizes the multifaceted nature of such trauma and the need to recognize anterior skull-base complications, including cerebrospinal fluid leak and brain injury.