Gerald J. Kutcher

A study of the effects of internal organ motion on dose escalation in conformal prostate treatments

BACKGROUND AND PURPOSEnTo assess the effect of internal organ motion on the dose distributions and biological indices for the target and non-target organs for three different conformal prostate treatment techniques.nnnMATERIALS AND METHODSnWe examined three types of treatment plans in 20 patients: (1) a six field plan, with a prescribed dose of 75.6 Gy; (2) the same six field plan to 72 Gy followed by a boost to 81 Gy; and (3) a five field plan with intensity modulated beams delivering 81 Gy. Treatment plans were designed using an initial CT data set (planning) and applied to three subsequent CT scans (treatment). The treatment CT contours were used to represent patient specific organ displacement; in addition, the dose distribution was convolved with a Gaussian distribution to model random setup error. Dose-volume histograms were calculated using an organ deformation model in which the movement between scans of individual points interior to the organs was tracked and the dose accumulated. The tumor control probability (TCP) for the prostate and proximal half of seminal vesicles (clinical target volume, CTV), normal tissue complication probability (NTCP) for the rectum and the percent volume of bladder wall receiving at least 75 Gy were calculated.nnnRESULTSnThe patient averaged increase in the planned TCP between plan types 2 and 1 and types 3 and 1 was 9.8% (range 4.9-12.5%) for both, whereas the corresponding increases in treatment TCP were 9.0% (1.3-16%) and 8.1% (-1.3-13.8%). In all patients, plans 2 and 3 (81 Gy) exhibited equal or higher treatment TCP than plan 1 (75.6 Gy). The maximum treatment NTCP for rectum never exceeded the planning constraint and percent volume of bladder wall receiving at least 75 Gy was similar in the planning and treatment scans for all three plans.nnnCONCLUSIONnFor plans that deliver a uniform prescribed dose to the planning target volume (PTV) (plan 1), current margins are adequate. In plans that further escalate the dose to part of the PTV (plans 2 and 3), in a fraction of the cases the CTV dose increase is less than planned, yet in all cases the TCP values are higher relative to the uniform dose PTV (plan 1). Doses to critical organs remain within the planning criteria.

Ultrasonic tissue characterization using 2-D spectrum analysis and its application in ocular tumor diagnosis.

We are investigating the utility of a new ultrasonic tissue characterization technique, specifically two-dimensional (2-D) spectrum analysis of radio-frequency backscatter signals, which promises to provide quantitative measures of the physical properties of tissue microstructures. Previously successful 1-D spectrum analysis is expanded to 2-D to more fully characterize diagnostically significant features of biological tissue. Two new spectral functions, radially integrated spectral power (RISP) and angularly integrated spectral power (AISP), are defined to quantitatively characterize tissue properties. This new approach is applied to the diagnosis of in vivo ocular melanomas. Our initial results indicate that 2-D spectrum analysis can provide significant new information on tissue anisotropy that are not apparent in 1-D spectra. Acoustic scattering models are applied to relate the 2-D spectral parameters to the physical properties (e.g., size and shape) of biological tissues.

Use of simulated annealing for optimization of alignment parameters in limited MRI acquisition volumes of the brain

Studies suggest that clinical outcomes are improved in repeat trigeminal neuralgia (TN) Gamma Knife radiosurgery if a different part of the nerve from the previous radiosurgery is treated. The MR images taken in the first and repeat radiosurgery need to be coregistered to map the first radiosurgery volume onto the second treatment planning image. We propose a fully automatic and robust three-dimensional (3-D) mutual information- (MI-) based registration method engineered by a simulated annealing (SA) optimization technique. Commonly, Powells method and Downhill simplex (DS) method are most popular in optimizing the MI objective function in medical image registration applications. However, due to the nonconvex property of the MI function, robustness of those two methods is questionable, especially for our cases, where only 28 slices of MR T1 images were utilized. Our SA method obtained successful registration results for all the 41 patients recruited in this study. On the other hand, Powells method and the DS method failed to provide satisfactory registration for 11 patients and 9 patients, respectively. The overlapping volume ratio (OVR) is defined to quantify the degree of the partial volume overlap between the first and second MR scan. Statistical results from a logistic regression procedure demonstrated that the probability of a success of Powells method tends to decrease as OVR decreases. The rigid registration with Powells or the DS method is not suitable for the TN radiosurgery application, where OVR is likely to be low. In summary, our experimental results demonstrated that the MI-based registration method with the SA optimization technique is a robust and reliable option when the number of slices in the imaging study is limited.

Ultrasonic tissue characterization via 2-D spectrum analysis: Theory and in vitro measurements

A theoretical model is described for application in ultrasonic tissue characterization using a calibrated 2-D spectrum analysis method. This model relates 2-D spectra computed from ultrasonic backscatter signals to intrinsic physical properties of tissue microstructures, e.g., size, shape, and acoustic impedance. The model is applicable to most clinical diagnostic ultrasound systems. Two experiments employing two types of tissue architectures, spherical and cylindrical scatterers, are conducted using ultrasound with center frequencies of 10 and 40 MHz, respectively. Measurements of a tissue-mimicking phantom with an internal suspension of microscopic glass beads are used to validate the theoretical model. Results from in vitro muscle fibers are presented to further elucidate the utility of 2-D spectrum analysis in ultrasonic tissue characterization.

Novel lung IMRT planning algorithms with nonuniform dose delivery strategy to account for respiratory motion.

To effectively deliver radiation dose to lung tumors, respiratory motion has to be considered in treatment planning. In this paper we first present a new lung IMRT planning algorithm, referred as the dose shaping (DS) method, that shapes the dose distribution according to the probability distribution of the tumor over the breathing cycle to account for respiratory motion. In IMRT planning a dose-based convolution method was generally adopted to compensate for random organ motion by performing 4-D dose calculations using a tumor motion probability density function. We modified the CON-DOSE method to a dose volume histogram based convolution method (CON-DVH) that allows nonuniform dose distribution to account for respiratory motion. We implemented the two new planning algorithms on an in-house IMRT planning system that uses the Eclipse (Varian, Palo Alto, CA) planning workstation as the dose calculation engine. The new algorithms were compared with (1) the conventional margin extension approach in which margin is generated based on the extreme positions of the tumor, (2) the dose-based convolution method, and (3) gating with 3 mm residual motion. Dose volume histogram, tumor control probability, normal tissue complication probability, and mean lung dose were calculated and used to evaluate the relative performance of these approaches at the end-exhale phase of the respiratory cycle. We recruited six patients in our treatment planning study. The study demonstrated that the two new methods could significantly reduce the ipsilateral normal lung dose and outperformed the margin extension method and the dose-based convolution method. Compared with the gated approach that has the best performance in the low dose region, the two methods we proposed have similar potential to escalate tumor dose, but could be more efficient because dose is delivered continuously.

Accurate colon residue detection algorithm with partial volume segmentation

Colon cancer is the second leading cause of cancer-related death in the United States. Earlier detection and removal of polyps can dramatically reduce the chance of developing malignant tumor. Due to some limitations of optical colonoscopy used in clinic, many researchers have developed virtual colonoscopy as an alternative technique, in which accurate colon segmentation is crucial. However, partial volume effect and existence of residue make it very challenging. The electronic colon cleaning technique proposed by Chen et al is a very attractive method, which is also kind of hard segmentation method. As mentioned in their paper, some artifacts were produced, which might affect the accurate colon reconstruction. In our paper, instead of labeling each voxel with a unique label or tissue type, the percentage of different tissues within each voxel, which we call a mixture, was considered in establishing a maximum a posterior probability (MAP) image-segmentation framework. A Markov random field (MRF) model was developed to reflect the spatial information for the tissue mixtures. The spatial information based on hard segmentation was used to determine which tissue types are in the specific voxel. Parameters of each tissue class were estimated by the expectation-maximization (EM) algorithm during the MAP tissue-mixture segmentation. Real CT experimental results demonstrated that the partial volume effects between four tissue types have been precisely detected. Meanwhile, the residue has been electronically removed and very smooth and clean interface along the colon wall has been obtained.

Implementation and validation of an ultrasonic tissue characterization technique for quantitative assessment of normal-tissue toxicity in radiation therapy

The goal of this study was to implement and validate a noninvasive, quantitative ultrasonic technique for accurate and reproducible measurement of normal-tissue toxicity in radiation therapy. The authors adapted an existing ultrasonic tissue characterization (UTC) technique that used a calibrated 1D spectrum based on region-of-interest analysis. They modified the calibration procedure by using a reference phantom instead of a planar reflector. This UTC method utilized ultrasonic radiofrequency echo signals to generate spectral parameters related to the physical properties (e.g., size, shape, and relative acoustic impedance) of tissue microstructures. Three spectral parameters were investigated for quantification of normal-tissue injury: Spectral slope, intercept, and midband fit. They conducted a tissue-mimicking phantom study to verify the reproducibility of UTC measurements and initiated a clinical study of radiation-induced breast-tissue toxicity. Spectral parameter values from measurements on two phantoms were reproducible within 1% of each other. Eleven postradiation breast-cancer patients were studied and significant differences between the irradiated and untreated (contralateral) breasts were observed for spectral intercept (p = 0.003) and midband fit (p < 0.001) but not for slope (p = 0.14). In comparison to the untreated breast, the average difference in the spectral intercept was 2.99 +/- 0.75 dB and the average difference in the midband fit was 3.99 +/- 0.65 dB. The preliminary clinical study demonstrated the feasibility of using the quantitative ultrasonic method to evaluate normal-tissue toxicity in radiation therapy.

Measurements of Radiation-Induced Skin Changes in Breast-Cancer Radiation Therapy Using Ultrasonic Imaging

Skin injury is a common side effect of breast- cancer radiation therapy. Although physicians often observe skin toxicity, quantifying its severity remains a challenge. We present a novel quantitative ultrasonic technique to evaluate skin changes associated with radiotherapy. An in vivo study with twelve breast- cancer patients was conducted. All patients received a standard course of post-surgery radiation therapy. Each patient received ultrasound scans to the irradiated breast and the untreated (contra-lateral) breast. Radio-frequency (RF) backscatter signals and B-mode images were acquired simultaneously. To quantify the severity of skin injury, two metrics were calculated from the RF signals: skin thickness and Pearson correlation coefficient of the subcutaneous layer. Comparing to the non-irradiated skin, the average thickness of the irradiated skin increased by 40% (p=0.005) and the average correlation coefficient of the irradiated hypodermis decreased by 35% (p=0.02). This study demonstrates the feasibility of using a non-invasive ultrasonic technique to detect and quantify radiation-induced skin changes.

Quality assurance in intensity modulated radiotherapy by identifying standards and patterns in treatment preparation: a feasibility study on prostate treatments.

BACKGROUND AND PURPOSEnQuality assurance (QA) in intensity modulated treatments is a complex and time-consuming process. In spite of intensive quality control procedures some types of errors still can go undetected through the course of a treatment. This study aims to develop an objective QA filter for fast, automatic detection of errors, based on the creation of a global platform monitoring treatment parameters by comparison with existing local standards. Since such a conceptually new type of QA has already proven successful for conventional treatments, we aim to extend it to intensity modulated radiotherapy (IMRT) treatments.nnnMATERIAL AND METHODSnThe feasibility of developing such a QA platform was evaluated on 12 prostate treatment plans. Apart from the classical treatment parameters, the optimised fluence distributions were compared and screened for repetitive patterns. This screening was performed by calculating specific parameters, defined to characterise the fluence maps.nnnRESULTSnRepetitive patterns were found in the beam shapes as well as in the intensity distributions, and useful parameters could be defined to quantify typical field patterns. By statistical analysis of these parameters, mean values and tolerance levels were derived, providing a means to automatically filter out unprobable or erroneous intensity modulated treatment fields during the treatment preparation stage.nnnCONCLUSIONnIt is possible to identify parameters quantifying the characteristic patterns found in fluence distributions of intensity modulated fields of a specific treatment, allowing the development of a platform for automatic pre-treatment quality control.

Incorporate Imaging Characteristics Into an Arteriovenous Malformation Radiosurgery Plan Evaluation Model

PURPOSEnTo integrate imaging performance characteristics, specifically sensitivity and specificity, of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) into arteriovenous malformation (AVM) radiosurgery planning and evaluation.nnnMETHODS AND MATERIALSnImages of 10 patients with AVMs located in critical brain areas were analyzed in this retrospective planning study. The image findings were first used to estimate the sensitivity and specificity of MRA and DSA. Instead of accepting the imaging observation as a binary (yes or no) mapping of AVM location, our alternative is to translate the image into an AVM probability distribution map by incorporating imagers sensitivity and specificity, and to use this map as a basis for planning and evaluation. Three sets of radiosurgery plans, targeting the MRA and DSA positive overlap, MRA positive, and DSA positive were optimized for best conformality. The AVM obliteration rate (ORAVM) and brain complication rate served as endpoints for plan comparison.nnnRESULTSnIn our 10-patient study, the specificities and sensitivities of MRA and DSA were estimated to be (0.95, 0.74) and (0.71, 0.95), respectively. The positive overlap of MRA and DSA accounted for 67.8% +/- 4.9% of the estimated true AVM volume. Compared with plans targeting MRA and DSA-positive overlap, plans targeting MRA-positive or DSA-positive improved ORAVM by 4.1% +/- 1.9% and 15.7% +/- 8.3%, while also increasing the complication rate by 1.0% +/- 0.8% and 4.4% +/- 2.3%, respectively.nnnCONCLUSIONSnThe impact of imagers quality should be quantified and incorporated in AVM radiosurgery planning and evaluation to facilitate clinical decision making.