Purpose: To investigate the possibility of using objective parameters in MRS of the prostate to identify areas of viable cancer that might need higher radiation therapy dose. Clinically, MRI and biopsy results may not always agree. MRS data can be very helpful in objectively defining a set of parameters that can positively identify cancerous regions. Method and Materials: Patients who are treated for prostate cancer using radiation therapy in our department are analyzed retrospectively. These patients are imaged using a GE 1.5T MRI scanner. T2‐weighted MRI images and MR spectroscopy are performed on these patients. MR spectroscopic data, in particular the ratio of Choline and Creatine to Citrate can be used to identify areas of the prostate, which could be boosted with additional dose since those areas are more prone to radiotherapy failure. In this study an attempt is made to define a set of parameters that will enable identifying areas of the prostate needing higher dose. As a first step, the correlation of biopsy‐positive data, MRS data, and expert reading of the T2‐weighted MR images by a radiologist is investigated. The prostate is divided into six parts, namely Right and Left parts of the Base, Mid, and Apex regions for this study. MRS data is gathered using the GE prostate protocol PROSE. An endorectal coil with the balloon filled with perflubrom is used in the MRS data acquisition. Results: Preliminary results from the analyses of four patients show a varied degree of correlation between the biopsy, MRS data, and the radiologist's readings although a minimum MRS ratio for the cutoff of cancer‐positive identification can be found. Conclusion: Objective cutoff parameters can be found for a population of prostate cancer patients to identify regions of the prostate, which are candidates for additional higher radiation dose.

Tibial dyschondroplasia (TD) is a metabolic cartilage disease of young poultry in which endochondral bone formation is disrupted leading to the retention of a non-calcified, avascular plug of cartilage in the tibial growth plate. Chicks aged 7 days were fed either a control diet or one containing thiram 100 ppm for 48 h to induce TD. Cell multiplication in the growth plate was determined thereafter with bromodeoxyuridine (BrdU) labelling, and metabolic changes by measuring alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), and glutathione (GSH) activities. The effect on chondrocyte maturation was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of gene expression. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) and DNA fragmentation were used to determine the effects of thiram on cell survival. The results showed that thiram-induced TD was not due to the multiplication of cells in the post-proliferative zones. Thiram did not affect ALP activity, which would have indicated a loss of calcification potential, but it reduced both TRAP and the glutathione concentrations, suggesting that the growth plate metabolism and remodelling functions were adversely affected. Thiram appeared to have no effect on the expression of type X collagen, transglutaminase, RUNX2, or matrix metalloproteinase-2 (MMP) genes suggesting that it did not alter the maturation potential of chondrocytes. On the contrary, the expressions of MMP-13 and vascular endothelial growth factor (VEGF) genes were “up-regulated,” suggesting that thiram has pro-angiogenic activity. However, TUNEL assay showed that thiram induced endothelial cell apoptosis in the capillary vessels of the growth plates, as early as 10 days of age, when TD was not visually evident. The vascular death increased on subsequent days accompanied by massive death of chondrocytes in the transition zone of the growth plate. The induction of apoptosis in the growth plate was also demonstrated by DNA fragmentation. It was concluded that thiram induced TD not through an increase in the multiplication of chondrocytes in the transition zone and not by altering the expression of genes causing the arrest of chondrocytes in a prehypertrophic state, but by creating a metabolic dysfunction which led to the destruction of blood capillaries in the transition zone chondrocytes.

Purpose: Accurate delineation of the gross tumor volume (GTV) is important in radiation therapy treatment planning. We evaluated the impact of PET and endoscopic ultrasound (EUS) compared with CT simulation in the planning of radiation fields for patients with esophageal carcinoma.Material and Methods: Twenty-five patients presenting with esophageal carcinoma for radiation therapy underwent PET scans in the treatment position after conventional CT simulation. Patients underwent PET/CT scanning after being injected with 10 to 20 mCi of [F-18]-2-deoxy-2-fluro-D-glucose. The length of the abnormality seen on the CT portion of the PET/CT scan vs. the PET scan alone was determined independently by 2 separate investigators. The length of the GTV and detection of regional adenopathy by PET was also correlated with EUS in 18 patients. Of the 18 patients who had EUS, 2 had T2 tumors and 16 had T3 tumors. Eighteen patients had adenocarcinoma and 7 had squamous cell carcinoma. Nine tumors were located at the gastroesophageal junction, 8 at the lower esophagus, 7 in the middle esophagus, and 1 in the cervical esophagus. The PET scans were reviewed to determine the length of the abnormality by use of a standard uptake value (SUV) of 2.5 to delineate the tumor extent.Results: The mean length of the cancer was 5.4 cm (95% CI 4.4-6.4 cm) as determined by PET scan, 6.77 cm (95% CI, 5.6-7.9 cm) as determined by CT scan, and 5.1 cm (95% CI, 4.0-6.1 cm) for the 22 patients who had endoscopy. The length of the tumors was significantly longer as measured by CT scans compared with PET scans (p = 0.0063). EUS detected significantly more patients with periesophageal and celiac lymphadenopathy compared to PET and CT. The SUV of the esophageal tumors was higher in patients with peri-esophageal lymphadenopathy identified on PET scans.Conclusion: Endoscopic ultrasound and PET scans can add additional information to aid the radiation oncologist's ability to precisely identify the GTV in patients with esophageal carcinoma. (c) 2005 Elsevier Inc.

PURPOSE:To quantify the three-dimensional intrafractional prostate motion over typical treatment time intervals with cine-magnetic resonance imaging (cine MRI) studies. METHODS AND MATERIALS:Forty-two patients with prostate cancer were scanned supine in an alpha cradle cast using cine MRI. Twenty sequential slices were acquired in the sagittal and axial planes through the center of the prostate. Each scan took approximately 9 min. The posterior, lateral, and superior edges of the prostate were tracked on each frame relative to the initial prostate position, and the size and duration of each displacement was recorded. RESULTS:The prostate displacements were (mean +/- SD): 0.2 +/- 2.9 mm, 0.0 +/- 3.4 mm, and 0.0 +/- 1.5 mm in the anterior-posterior, superior-inferior, and medial-lateral dimensions respectively. The prostate motion appeared to have been driven by peristalsis in the rectum. Large displacements of the prostate (up to 1.2 cm) moved the prostate both anteriorly and superiorly and in some cases compressed the organ. For such motions, the prostate did not stay displaced, but moved back to its original position. To account for the dosimetric consequences of the motion, we also calculated the time-averaged displacement to be approximately 1 mm. CONCLUSIONS:Cine MRI can be used to measure intrafractional prostate motion. Although intrafractional prostate motions occur, their effects are negligible compared to interfractional motion and setup error. No adjustment in margin is necessary for three-dimensional conformal or intensity-modulated radiation therapy.

PURPOSE:To quantify the dosimetric consequences of external patient contour distortions produced on low-field and high-field MRIs for external beam radiation of prostate cancer. METHODS AND MATERIALS:A linearity phantom consisting of a grid filled with contrast material was scanned on a spiral CT, a 0.23 T open MRI, and a 1.5 T closed bore system. Subsequently, 12 patients with prostate cancer were scanned on CT and the open MRI. A gradient distortion correction (GDC) program was used to postprocess the MRI images. Eight of the patients were also scanned on the 1.5 T MRI with integrated GDC correction. All data sets were fused according to their bony landmarks using a chamfer-matching algorithm. The prostate volume was contoured on an MRI image, irrespective of the apparent prostate location in those sets. Thus, the same target volume was planned and used for calculating the anterior-posterior (AP) and lateral separations. The number of monitor units required for treatment using a four-field conformal technique was compared. Because there are also setup variations in patient outer contours, two different CT scans from 20 different patients were fused, and the differences in AP and lateral separations were measured to obtain an estimate of the mean interfractional separation variation. RESULTS:All AP separations measured on MRI were statistically indistinguishable from those on CT within the interfractional separation variations. The mean differences between CT and low-field MRI and CT and high-field MRI lateral separations were 1.6 cm and 0.7 cm, respectively, and were statistically significantly different from zero. However, after the GDC was applied to the low-field images, the difference became 0.4 +/- 0.4 mm (mean +/- standard deviation), which was statistically insignificant from the CT-to-CT variations. The mean variations in the lateral separations from the low-field images with GDC would result in a dosimetric difference of <1%, assuming an equally weighted four-field 18-MV technique for patient separations up to approximately 40 cm. CONCLUSIONS:For patients with lateral separations <40 cm, a homogeneous calculation simulated using a 1.5 T MRI or a 0.23 T MRI with a gradient distortion correction will yield a monitor unit calculation indistinguishable from that generated using CT simulation.

Purpose: Conformal external beam radiation and IMRT for prostate cancer are planned primarily based upon CT. MRI has been shown to permit more accurate delineation of the prostate than CT. The purpose of this study was to determine the impact of MRI delineation on target coverage, treatment time, and dose to the bladder and rectum for IMRT in prostate cancer. Materials and Methods: From 2/01-3/01, all patients with prostate cancer treated by three of the authors with conformal external beam radiation underwent routine MRI scanning. The study population consists of 8 of 13 patients chosen for IMRT because of one or more of the following characteristics: PSA > 10 ng/ml, Gleason 7-10, palpable T2B or T3 tumor, or presence of perineural invasion. All underwent CT simulation followed by an MRI using a dedicated open 0.23 T unit in the supine casted treatment position. The prostate, bladder and rectum were delineated first on CT. The studies were fused and the MRI was used to redefine the internal anatomy. Both sets of contours were input into an inverse planning system. For each patient a separate IMRT treatment plan was performed based upon the CT and MRI defined prostate, bladder and rectum. The 16 treatment plans for IMRT were accepted after 45 iterations. This included two sets of plans for one patient who had required a repeat scan after hormonal therapy to meet acceptance criteria. All patients were initially treated to 56 Gy using a four field conformal technique. The planning target volume (PTV) of prostate plus margin of 5 mm was then treated for 23 Gy using IMRT. Results: The MRI-based prostate volumes were larger than on CT for 4 of 8 patients (mean 39.4 cc vs. 34.7 cc, 13.5% increase) with a range of −12.4% to 64.6% (mean 18.3%, median 3.4%). There was no significant difference in treatment planning time required between CT and MRI data sets. Most patients required the same number of beam orientations (5) and iterations (median 1.5) to derive a solution for each data set. In general the MRI-based plans required slight alterations of beam directions to increase separation between the MRI-PTV, bladder and rectum. There was a modest increase in the mean number of segments (35 vs. 38) for the MRI-PTV plans, so that the mean total treatment time was increased by 48 seconds. There was no difference in the dose inhomogeneity between CT and MRI plans (mean 115.7% vs. 116%, median 115.1% vs. 115.1%). Since MRI produces more accurate delineation of the prostate, the coverage of the MRI-PTV with the plan based upon the CT contours represents the potential miss in target coverage if CT alone were used. Dose-volume histogram analysis revealed that the plans generated from the CT data set resulted in coverage of 95% of the MRI-PTV by a mean of 80.0% of the dose (range 56.8%-93.4%, median 80.4%). This compares to a mean of 96.8% of the dose (range 91.8%-100.9%, median 96.6%) covering 95% of the MRI-PTV by the plans generated from the MRI data set. The mean dose received by 20% of the rectum was 59.6% for the CT plans and 60.2% (range 51%-67%) for the MRI plans. The mean dose received by 20% of the bladder was 44.7% and 44.6% (range 23.6%-52.6%) between CT and MRI-based plans respectively. Conclusion: The use of MRI simulation added significantly to the coverage of the PTV during IMRT compared to CT simulation alone. Despite a larger delineation of the prostate by MRI compared with CT, the MRI-based treatment plans did not result in increased dose to the bladder or rectum. There was also no significant increase in planning or overall treatment time with MRI-based plans. The routine use of MRI simulation is a feasible means of improving the therapeutic ratio for IMRT and high dose conformal external beam radiation for prostate cancer.