Partial volume correction incorporating Rb-82 positron range for quantitative myocardial perfusion PET based on systolic-diastolic activity ratios and phantom measurements.

BACKGROUND: Quantitative myocardial PET perfusion imaging requires partial volume corrections. METHODS: Patients underwent ECG-gated, rest-dipyridamole, myocardial perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and combined whole cycle ungated images. Diastolic partial volume correction relative to systole was determined from the systolic/diastolic activity ratio, systolic partial volume correction from phantom dimensions comparable to systolic LV wall thicknesses and whole heart cycle partial volume correction for ungated images from fractional systolic-diastolic duration for systolic and diastolic partial volume corrections. RESULTS: For 264 PET perfusion images from 159 patients (105 rest-stress image pairs, 54 individual rest or stress images), average resting diastolic partial volume correction relative to systole was 1.14 ± 0.04, independent of heart rate and within ±1.8% of stress images (1.16 ± 0.04). Diastolic partial volume corrections combined with those for phantom dimensions comparable to systolic LV wall thickness gave an average whole heart cycle partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14 if positron range were negligible as for F-18. CONCLUSION: Quantitative myocardial PET perfusion imaging requires partial volume correction, herein demonstrated clinically from systolic/diastolic absolute activity ratios combined with phantom data accounting for Rb-82 positron range.

Verification of the clinical implementation of the respiratory gated beam delivery technique with synchrotron-based proton irradiation

The clinical advantage for protons over conventional high-energy x-rays stems from their unique depth-dose distribution, which delivers essentially no dose beyond the end of range. In order to achieve it, accurate localization of the tumor volume relative to the proton beam is necessary. For cases where the tumor moves with respiration, the resultant dose distribution is sensitive to such motion. One way to reduce uncertainty caused by respiratory motion is to use gated beam delivery. The main goal of this dissertation is to evaluate the respiratory gating technique in both passive scattering and scanning delivery mode. Our hypothesis for the study was that optimization of the parameters of synchrotron operation and respiratory gating can lead to greater efficiency and accuracy of respiratory gating for all modes of synchrotron-based proton treatment delivery. The hypothesis is tested in two specific aims. The specific aim #1 is to assess the efficiency of respiratory-gated proton beam delivery and optimize the synchrotron operations for the gated proton therapy. A simulation study was performed and introduced an efficient synchrotron operation pattern, called variable Tcyc. In addition, the simulation study estimated the efficiency in the respiratory gated scanning beam delivery mode as well. The specific aim #2 is to assess the accuracy of beam delivery in respiratory-gated proton therapy. The simulation study was extended to the passive scattering mode to estimate the quality of pulsed beam delivery to the residual motion for several synchrotron operation patterns with the gating technique. The results showed that variable Tcyc operation can offer good reproducible beam delivery to the residual motion at a certain phase of the motion. For respiratory gated scanning beam delivery, the impact of motion on the dose distributions by scanned beams was investigated by measurement. The results showed the threshold for motion for a variety of scan patterns and the proper number of paintings for normal and respiratory gated beam deliveries. The results of specific aims 1 and 2 provided supporting data for implementation of the respiratory gating beam delivery technique into both passive and scanning modes and the validation of the hypothesis.

RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER

Purpose: The rapid distal falloff of a proton beam allows for sparing of normal tissues distal to the target. However proton beams that aim directly towards critical structures are avoided due to concerns of range uncertainties, such as CT number conversion and anatomy variations. We propose to eliminate range uncertainty and enable prostate treatment with a single anterior beam by detecting the proton’s range at the prostate-rectal interface and adaptively adjusting the range in vivo and in real-time. Materials and Methods: A prototype device, consisting of an endorectal liquid scintillation detector and dual-inverted Lucite wedges for range compensation, was designed to test the feasibility and accuracy of the technique. Liquid scintillation filled volume was fitted with optical fiber and placed inside the rectum of an anthropomorphic pelvic phantom. Photodiode-generated current signal was generated as a function of proton beam distal depth, and the spatial resolution of this technique was calculated by relating the variance in detecting proton spills to its maximum penetration depth. The relative water-equivalent thickness of the wedges was measured in a water phantom and prospectively tested to determine the accuracy of range corrections. Treatment simulation studies were performed to test the potential dosimetric benefit in sparing the rectum. Results: The spatial resolution of the detector in phantom measurement was 0.5 mm. The precision of the range correction was 0.04 mm. The residual margin to ensure CTV coverage was 1.1 mm. The composite distal margin for 95% treatment confidence was 2.4 mm. Planning studies based on a previously estimated 2mm margin (90% treatment confidence) for 27 patients showed a rectal sparing up to 51% at 70 Gy and 57% at 40 Gy relative to IMRT and bilateral proton treatment. Conclusion: We demonstrated the feasibility of our design. Use of this technique allows for proton treatment using a single anterior beam, significantly reducing the rectal dose.

Long range physical map of the Wilms' tumor - aniridia region on human chromosome 11

Nephroblastoma or Wilms' tumor is a pediatric renal malignancy that is the most frequently occurring childhood solid tumor. Approximately 1-2% of children with Wilms' tumor also present with aniridia, a congenital absence of all or part of the iris of the eye. These children also have high rates of genitourinary anomalies and mental retardation resulting in what is called the WAGR (Wilms' tumor, aniridia, genitourinary anomaly, mental retardation) syndrome. Cytogenetic analysis of metaphase chromosomes from these patients revealed a consistent deletion of band P13 on chromosome 11. These observations suggest close physical linkage between the disease-related loci, and further imply that development of each phenotype results from the loss of normal gene function.^ The objective of this work is to understand the molecular events at chromosome band 11p13 that are essential to the development of sporadic Wilms' tumor and sporadic aniridia. Two human/hamster somatic cell hybrids have been used to identify sixteen independent DNA probes that map to this segment of the human genome. These newly identified DNA probes and four previously reported probes (CAT, FSHB, D11S16, and HBVIS) have been used to subdivide 11p13 into five intervals defined by overlapping constitutional deletions from several WAGR patients. A long-range physical map of 11p13 has been constructed using each of these probes in Southern blot analysis of genomic DNA after digestion with infrequently cutting restriction enzymes and pulse-field gel electrophoresis. This map, established primarily with MluI and NotI, spans approximately 13 $\times$ 10$\sp{6}$ bp and encompasses deletion and translocation breakpoints associated with genitourinary anomalies, aniridia, and sporadic Wilms' tumor. This complete physical map of human chromosome band 11p13 enables us to localize the genes for sporadic Wilms' tumor and sporadic aniridia to a small number of specific NotI fragments. ^