Genomic profiling in locally advanced and inflammatory breast cancer and its link to DCE-MRI and overall survival.

PURPOSE: We have previously reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns obtained from locally advanced breast cancer (LABC) patients prior to neoadjuvant therapy predicted pathologic clinical response. Genomic analyses were also independently conducted on the same patient population. This retrospective study was performed to test two hypotheses: (1) gene expression profiles are associated with DCE-MRI perfusion patterns, and (2) association between long-term overall survival data and gene expression profiles can lead to the identification of novel predictive biomarkers. METHODS: We utilised RNA microarray and DCE-MRI data from 47 LABC patients, including 13 inflammatory breast cancer (IBC) patients. Association between gene expression profile and DCE-MRI perfusion patterns (centrifugal and centripetal) was determined by Wilcoxon rank sum test. Association between gene expression level and survival was assessed using a Cox rank score test. Additional genomic analysis of the IBC subset was conducted, with a period of follow-up of up to 11 years. Associations between gene expression and overall survival were further assessed in The Cancer Genome Atlas Data Portal. RESULTS: Differences in gene expression profiles were seen between centrifugal and centripetal perfusion patterns in the sulphotransferase family, cytosolic, 1 A, phenol-preferring, members 1 and 2 (SULT1A1, SULT1A2), poly (ADP-ribose) polymerase, member 6 (PARP6), and metastasis tumour antigen1 (MTA1). In the IBC subset our analyses demonstrated that differential expression of 45 genes was associated with long-term survival. CONCLUSIONS: Here we have demonstrated an association between DCE-MRI perfusion patterns and gene expression profiles. In addition we have reported on candidate prognostic biomarkers in IBC patients, with some of the genes being significantly associated with survival in IBC and LABC.

Diffusion-weighted imaging for head and neck squamous cell carcinoma: quantifying repeatability to understand early treatment-induced change.

OBJECTIVE: The purpose of this study was to define baseline variability of apparent diffusion coefficient (ADC) on diffusion-weighted MR imaging (DWI) in patients with head and neck squamous cell carcinoma (HNSCC) and to compare it with early treatment-induced ADC change. SUBJECTS AND METHODS: Patients with American Joint Committee on Cancer stages III and IV HNSCC were imaged with two baseline DWI examinations 1 week apart and a third DWI examination during the 2nd week of curative-intent chemoradiation therapy. Mean ADC was measured in the primary tumor and largest lymph node for each patient on the three DWI scans. Mean baseline percentage differences (%∆ADC) were compared with intratreatment change. The repeatability coefficient for baseline %∆ADC was calculated and compared with intratreatment %∆ADC. Repeatability was also assessed with Bland-Altman plots and the intraclass correlation coefficient (ICC). RESULTS: Sixteen patients underwent double baseline imaging, with 14 also undergoing intratreatment imaging. Baseline nodal disease ADC could be measured in 16 patients, but ADC in primary tumors could only be measured in five patients. The nodal mean (SD) baseline %∆ADC was 8% (± 7%), which was significantly different compared with intratreatment changes of 32% (± 31%) (p = 0.01). Baseline ICC was 0.86 for nodal disease and 0.99 for primary tumor (excellent correlation). The calculated repeatability coefficient for baseline nodal ADC was 15%. No patients had decreases in intratreatment ADC of more than 15%. CONCLUSION: Baseline ADC variability for HNSCC is less than intratreatment ADC change for nodal disease. Assessment of response should consider intrinsic baseline variability.

Comprehensive population-averaged arterial input function for dynamic contrast-enhanced vmagnetic resonance imaging of head and neck cancer.

PURPOSE: To generate a population-averaged arterial input function (PA-AIF) for quantitative analysis of dynamic contrast-enhanced MRI data in head and neck cancer patients. METHODS AND MATERIALS: Twenty patients underwent dynamic contrast-enhanced MRI during concurrent chemoradiation therapy. Imaging consisted of 2 baseline scans 1 week apart (B1/B2) and 1 scan after 1 week of chemoradiation therapy (Wk1). Regions of interest (ROIs) in the right and left carotid arteries were drawn on coronal images. Plasma concentration curves of all ROIs were averaged and fit to a biexponential decay function to obtain the final PA-AIF (AvgAll). Right-sided and left-sided ROI plasma concentration curves were averaged separately to obtain side-specific AIFs (AvgRight/AvgLeft). Regions of interest were divided by time point to obtain time-point-specific AIFs (AvgB1/AvgB2/AvgWk1). The vascular transfer constant (Ktrans) and the fractional extravascular, extracellular space volume (Ve) for primaries and nodes were calculated using the AvgAll AIF, the appropriate side-specific AIF, and the appropriate time-point-specific AIF. Median Ktrans and Ve values derived from AvgAll were compared with those obtained from the side-specific and time-point-specific AIFs. The effect of using individual AIFs was also investigated. RESULTS: The plasma parameters for AvgAll were a1,2 = 27.11/17.65 kg/L, m1,2 = 11.75/0.21 min(-1). The coefficients of repeatability (CRs) for AvgAll versus AvgLeft were 0.04 min(-1) for Ktrans and 0.02 for Ve. For AvgAll versus AvgRight, the CRs were 0.08 min(-1) for Ktrans and 0.02 for Ve. When AvgAll was compared with AvgB1/AvgB2/AvgWk1, the CRs were slightly higher: 0.32/0.19/0.78 min(-1), respectively, for Ktrans; and 0.07/0.08/0.09 for Ve. Use of a PA-AIF was not significantly different from use of individual AIFs. CONCLUSION: A PA-AIF for head and neck cancer was generated that accounts for differences in right carotid artery versus left carotid artery, day-to-day fluctuations, and early treatment-induced changes. The small CRs obtained for Ktrans and Ve indicate that side-specific AIFs are not necessary. However, a time-point-specific AIF may improve pharmacokinetic accuracy.

Preclinical assessment of comfort and secure fit of thermobrachytherapy surface applicator (TBSA) on volunteer subjects.

A thermobrachytherapy surface applicator (TBSA) was developed for simultaneous heat and brachytherapy treatment of chest wall (CW) recurrence of breast cancer. The ability to comfortably secure the applicator over the upper torso relative to the CW target throughout treatment is assessed on volunteers. Male and postmastectomy female volunteers were enrolled to evaluate applicator secure fit to CW. Female subjects with intact breast were also enrolled to assess the ability to treat challenging cases. Magnetic resonance (MR) images of volunteers wearing a TBSA over the upper torso were acquired once every 15 minutes for 90 minutes. Applicator displacement over this time period required for treatment preplanning and delivery was assessed using MR visible markers. Applicator comfort and tolerability were assessed using a questionnaire. Probability estimates of applicator displacements were used to investigate dosimetric impact for the worst-case variation in radiation source-to-skin distance for 5 and 10 mm deep targets spread 17 × 13 cm on a torso phantom. Average and median displacements along lateral and radial directions were less than 1.2 mm over 90 minutes for all volunteers. Maximum lateral and radial displacements were measured to be less than 1 and 1.5 mm, respectively, for all CW volunteers and less than 2 mm for intact breast volunteers, excluding outliers. No complaint of pain or discomfort was reported. Phantom treatment planning for the maximum displacement of 2 mm indicated < 10% increase in skin dose with < 5% loss of homogeneity index (HI) for -2 mm uniform HDR source displacement. For +2 mm uniform displacement, skin dose decreased and HI increased by 20%. The volunteer study demonstrated that such large and uniform displacements should be rare for CW subjects, and the measured variation is expected to be low for multifraction conformal brachytherapy treatment.

Utility of treatment planning for thermochemotherapy treatment of nonmuscle invasive bladder carcinoma.

PURPOSE: A recently completed Phase I clinical trial combined concurrent Mitomycin-C chemotherapy with deep regional heating using BSD-2000 Sigma-Ellipse applicator (BSD Corporation, Salt Lake City, UT, U.S.A.) for the treatment of nonmuscle invasive bladder cancer. This work presents a new treatment planning approach, and demonstrates potential impact of this approach on improvement of treatment quality. METHODS: This study retrospectively analyzes a subset of five patients on the trial. For each treatment, expert operators selected "clinical-optimal" settings based on simple model calculation on the BSD-2000 control console. Computed tomography (CT) scans acquired prior to treatment were segmented to create finite element patient models for retrospective simulations with Sigma-HyperPlan (Dr. Sennewald Medizintechnik GmbH, Munchen, Germany). Since Sigma-HyperPlan does not account for the convective nature of heat transfer within a fluid filled bladder, an effective thermal conductivity for bladder was introduced. This effective thermal conductivity value was determined by comparing simulation results with clinical measurements of bladder and rectum temperatures. Regions of predicted high temperature in normal tissues were compared with patient complaints during treatment. Treatment results using "computed-optimal" settings from the planning system were compared with clinical results using clinical-optimal settings to evaluate potential of treatment improvement by reducing hot spot volume. RESULTS: For all five patients, retrospective treatment planning indicated improved matches between simulated and measured bladder temperatures with increasing effective thermal conductivity. The differences were mostly within 1.3 °C when using an effective thermal conductivity value above 10 W/K/m. Changes in effective bladder thermal conductivity affected surrounding normal tissues within a distance of ∼1.5 cm from the bladder wall. Rectal temperature differences between simulation and measurement were large due to sensitivity to the sampling locations in rectum. The predicted bladder T90 correlated well with single-point bladder temperature measurement. Hot spot locations predicted by the simulation agreed qualitatively with patient complaints during treatment. Furthermore, comparison between the temperature distributions with clinical and computed-optimal settings demonstrated that the computed-optimal settings resulted in substantially reduced hot spot volumes. CONCLUSIONS: Determination of an effective thermal conductivity value for fluid filled bladder was essential for matching simulation and treatment temperatures. Prospectively planning patients using the effective thermal conductivity determined in this work can potentially improve treatment efficacy (compared to manual operator adjustments) by potentially lower discomfort from reduced hot spots in normal tissue.

Dynamic contrast-enhanced MRI in head-and-neck cancer: the impact of region of interest selection on the intra- and interpatient variability of pharmacokinetic parameters.

PURPOSE: Dynamic contrast-enhanced (DCE) MRI-extracted parameters measure tumor microvascular physiology and are usually calculated from an intratumor region of interest (ROI). Optimal ROI delineation is not established. The valid clinical use of DCE-MRI requires that the variation for any given parameter measured within a tumor be less than that observed between tumors in different patients. This work evaluates the impact of tumor ROI selection on the assessment of intra- and interpatient variability. METHOD AND MATERIALS: Head and neck cancer patients received initial targeted therapy (TT) treatment with erlotinib and/or bevacizumab, followed by radiotherapy and concurrent cisplatin with synchronous TT. DCE-MRI data from Baseline and the end of the TT regimen (Lead-In) were analyzed to generate the vascular transfer function (K(trans)), the extracellular volume fraction (v(e)), and the initial area under the concentration time curve (iAUC(1 min)). Four ROI sampling strategies were used: whole tumor or lymph node (Whole), the slice containing the most enhancing voxels (SliceMax), three slices centered in SliceMax (Partial), and the 5% most enhancing contiguous voxels within SliceMax (95Max). The average coefficient of variation (aCV) was calculated to establish intrapatient variability among ROI sets and interpatient variability for each ROI type. The average ratio between each intrapatient CV and the interpatient CV was calculated (aRCV). RESULTS: Baseline primary/nodes aRCVs for different ROIs not including 95Max were, for all three MR parameters, in the range of 0.14-0.24, with Lead-In values between 0.09 and 0.2, meaning a low intrapatient vs. interpatient variation. For 95Max, intrapatient CVs approximated interpatient CVs, meaning similar data dispersion and higher aRCVs (0.6-1.27 for baseline) and 0.54-0.95 for Lead-In. CONCLUSION: Distinction between different patient's primary tumors and/or nodes cannot be made using 95Max ROIs. The other three strategies are viable and equivalent for using DCE-MRI to measure head and neck cancer physiology.

Commissioning of Varian ring & tandem HDR applicators: reproducibility and interobserver variability of dwell position offsets.

Studies have shown that source dwells within Varian's HDR CT/MR compatible ring applicators can deviate from intended positions by several millimeters. Quantifying this offset is an important part of commissioning. The aims of this study were to: 1) determine the reproducibility of the offset, 2) study the interobserver variation in the offset's measurement, and 3) quantify the dosimetric impact of the offset. Offsets were measured for four ring applicators: two 30°, one 45°, and one 60°. Dwell positions were measured five times for each ring to determine the reproducibility of source positioning. Experiments were done to compare two separate source wires, as well as different time points within a single source wire's lifecycle. Data were analyzed by three independent observers. To quantify the dosimetric impact of the offset, a treatment plan was generated using BrachyVision. The dose to point A, and the D(2cc) metric for rectum and bladder were calculated with and without the offset. For the 45° and 60° rings, measured offsets were 3.0 mm and 3.6 mm, respectively. The 30° ring showed substantial variation in distal dwell positions (maximum difference between the five experiments of 2.9 mm). Subsequent testing of a replacement ring showed an offset of 2.4 mm that was more reproducible. Offsets varied less than 1 mm between different source wires, and changed less than 1 mm over the course of a source wire's lifecycle. When comparing observers, the average range in a measurement of a dwell position was 0. 5 mm (σ = 0.2 mm, max 1.3 mm). The offset resulted in dose variations to point A, bladder, and rectum of less than 1%, 2%, and 5%, respectively. Results indicate that Varian rings can show systematic and random offsets of more than 3 mm. Some can be considered defective and should be replaced. Each applicator should be individually commissioned and reproducibility should be confirmed with multiple tests.

Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplantation trial.

PURPOSE: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. METHODS AND MATERIALS: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34(+) selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. RESULTS: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. CONCLUSIONS: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.

Improved hyperthermia treatment control using SAR/temperature simulation and PRFS magnetic resonance thermal imaging.

PURPOSE: This article explores the feasibility of using coupled electromagnetic and thermodynamic simulations to improve planning and control of hyperthermia treatments for cancer. The study investigates the usefulness of preplanning to improve heat localisation in tumour targets in treatments monitored with PRFS-based magnetic resonance thermal imaging (MRTI). METHODS: Heating capabilities of a cylindrical radiofrequency (RF) mini-annular phased array (MAPA) applicator were investigated with electromagnetic and thermal simulations of SAR in homogeneous phantom models and two human leg sarcomas. High frequency structure simulator (HFSS) (Ansoft) was used for electromagnetic simulations and SAR patterns were coupled into EPhysics (Ansoft) for thermal modelling with temperature-dependent variable perfusion. Simulations were accelerated by integrating tumour-specific anatomy into a pre-gridded whole body tissue model. To validate this treatment planning approach, simulations were compared with MR thermal images in both homogenous phantoms and heterogeneous tumours. RESULTS: SAR simulations demonstrated excellent agreement with temperature rise distributions obtained with MR thermal imaging in homogeneous phantoms and clinical treatments of large soft-tissue sarcomas. The results demonstrate feasibility of preplanning appropriate relative phases of antennas for localising heat in tumour. CONCLUSIONS: Advances in the accuracy of computer simulation and non-invasive thermometry via MR thermal imaging have provided powerful new tools for optimisation of clinical hyperthermia treatments. Simulations agree well with MR thermal images in both homogeneous tissue models and patients with lower leg tumours. This work demonstrates that better quality hyperthermia treatments should be possible when simplified hybrid model simulations are performed routinely as part of the clinical pretreatment plan.

Hyperthermia combined with radiation therapy for superficial breast cancer and chest wall recurrence: a review of the randomised data.

Hyperthermia has long been used in combination with radiation for the treatment of superficial malignancies, in part due to its radiosensitising capabilities. Patients who suffer superficial recurrences of breast cancer, be it in their chest wall following mastectomy, or in their breast after breast conservation, typically have poor clinical outcomes. They often develop distant metastatic disease, but one must not overlook the problems associated with an uncontrolled local failure. Morbidity is enormous, and can significantly impair quality of life. There is no accepted standard of care in treating superficial recurrences of breast cancer, particularly in patients that have previously been irradiated. There is a substantial literature regarding the combined use of hyperthermia and radiotherapy for these superficial recurrences. Most of it is retrospective in nature, but there are several larger phase III randomised trials that show an improved rate of clinical complete response in patients treated with both modalities. In this review article, we will highlight the important prospective data that has been published regarding the combined use of hyperthermia and radiation.

Hyperthermia for locally advanced breast cancer.

Hyperthermia (HT) has a proven benefit for treating superficial malignancies, particularly chest wall recurrences of breast cancer. There has been less research utilising HT in patients with locally advanced breast cancer (LABC), but available data are promising. HT has been combined with chemotherapy and/or radiotherapy in the neoadjuvant, definitive and adjuvant setting, albeit in series with small numbers of patients. There is only one phase III trial that examines hyperthermia in LABC, also with relatively small numbers of patients. The goal of this review is to highlight important research utilising HT in patients with LABC as well as to suggest future directions for its use.

Magnetic resonance imaging: a potential tool in assessing the addition of hyperthermia to neoadjuvant therapy in patients with locally advanced breast cancer.

The poor overall survival for patients with locally advanced breast cancers has led over the past decade to the introduction of numerous neoadjuvant combined therapy regimens to down-stage the disease before surgery. At the same time, more evidence suggests the need for treatment individualisation with a wide variety of new targets for cancer therapeutics and also multi modality therapies. In this context, early determination of whether the patient will fail to respond can enable the use of alternative therapies that can be more beneficial. The purpose of this review is to examine the potential role of magnetic resonance imaging (MRI) in early prediction of treatment response and prognosis of overall survival in locally advanced breast cancer patients enrolled on multi modality therapy trials that include hyperthermia. The material is organised with a review of dynamic contrast (DCE)-MRI and diffusion weighted (DW)-MRI for characterisation of phenomenological parameters of tumour physiology and their potential role in estimating therapy response. Most of the work published in this field has focused on responses to neoadjuvant chemotherapy regimens alone, so the emphasis will be there, however the available data that involves the addition of hyperthermia to the regimen will be discussed The review will also include future directions that include the potential use of MRI imaging techniques in establishing the role of hyperthermia alone in modifying breast tumour microenvironment, together with specific challenges related to performing such studies.

Accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas.

PURPOSE: To establish accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas. METHODS: Protocol patients with advanced extremity sarcomas were treated with external beam radiation therapy and hyperthermia. Invasive temperature measures were compared to noninvasive magnetic resonance thermal imaging (MRTI) at 1.5 T performed during hyperthermia. Volumetric temperature rise images were obtained using the proton resonance frequency shift (PRFS) technique during heating in a 140 MHz miniannular phased array applicator. MRTI temperature changes were compared to invasive measurements of temperature with a multisensor fiber optic probe inside a #15 g catheter in the tumor. Since the PRFS technique is sensitive to drifts in the primary imaging magnetic field, temperature change distributions were corrected automatically during treatment using temperature-stable reference materials to characterize field changes in 3D. The authors analyzed MRT images and compared, in evaluable treatments, MR-derived temperatures to invasive temperatures measured in extremity sarcomas. Small regions of interest (ROIs) were specified near each invasive sensor identified on MR images. Temperature changes in the interstitial sensors were compared to the corresponding ROI PRFS-based temperature changes over the entire treatment and over the steady-state period. Nonevaluable treatments (motion/imaging artifacts, noncorrectable drifts) were not included in the analysis. RESULTS: The mean difference between MRTI and interstitial probe measurements was 0.91 degrees C for the entire heating time and 0.85 degrees C for the time at steady state. These values were obtained from both tumor and normal tissue ROIs. When the analysis is done on just the tumor ROIs, the mean difference for the whole power on time was 0.74 degrees C and during the period of steady state was 0.62 degrees C. CONCLUSIONS: The data show that for evaluable treatments, excellent correlation (deltaT < 1 degrees C) of MRTI-ROI and invasive measurements can be achieved, but that motion and other artifacts are still serious challenges that must be overcome in future work.

DCE-MRI parameters have potential to predict response of locally advanced breast cancer patients to neoadjuvant chemotherapy and hyperthermia: a pilot study.

UNLABELLED: Combined therapies represent a staple of modern medicine. For women treated with neoadjuvant chemotherapy (NA ChT) for locally advanced breast cancer (LABC), early determination of whether the patient will fail to respond can enable the use of alternative, more beneficial therapies. This is even more desirable when the combined therapy includes hyperthermia (HT), an efficient way to improve drug delivery, however, more costly and time consuming. There is data showing that this goal can be achieved using magnetic resonance imaging (MRI) with contrast agent (CA) enhancement. This work for the first time proposes combining the information extracted from pre-treatment MR imaging into a morpho-physiological tumour score (MPTS) with the hypothesis that this score will increase the prognostic efficacy, compared to each of its MR-derived components: morphological (derived from the shape of the tumour enhancement) and physiological (derived from the CA enhancement variance dynamics parameters). The MPTS was correlated with response as determined by both pathologic residual tumour and MRI imaging, and was shown to have potential to predict response. The MPTS was extracted from pre-treatment MRI parameters, so independent of the combined therapy used. PURPOSE: To use a novel morpho-physiological tumour score (MPTS) generated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict response to treatment. MATERIALS AND METHODS: A protocol was designed to acquire DCE-MRI images of 20 locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NA ChT) and hyperthermia (HT). Imaging was done over 30 min following bolus injection of gadopentetate-based contrast agent. Parametric maps were generated by fitting the signal intensity to a double exponential curve and were used to derive a morphological characterisation of the lesions. Enhancement-variance dynamics parameters, wash-in and wash-out parameters (WiP, WoP), were extracted. The morphological characterisation and the WiP and WoP were combined into a MPTS with the intent of achieving better prognostic efficacy. The MPTS was correlated with response to NA therapy as determined by pathological residual tumour and MRI imaging. RESULTS: The contrast agent in all tumours typically peaked in the first 1-4 min. The tumours' WiP and WoP varied considerably. The MPTS was highly correlated with whether the patients had a pathological response. This scoring system has a specificity of 78% and a sensitivity of 91% for predicting response to NA chemotherapy. The kappa was 0.69 with a 95% confidence interval of [0.38, 1] and a p-value of 0.002. CONCLUSIONS: This pilot study shows that the MPTS derived using pre-treatment MRI images has the potential to predict response to NA ChT and HT in LABC patients. Further prospective studies are needed to confirm the validity of these results.

Progress on ThermoBrachytherapy Surface Applicator for Superficial Tissue Diseases.

This work reports the ongoing development of a combination applicator for simultaneous heating of superficial tissue disease using a 915 MHz DCC (dual concentric conductor) array and High Dose Rate (HDR) brachytherapy delivered via an integrated conformal catheter array. The progress includes engineering design changes in the waterbolus, DCC configurations and fabrication techniques of the conformal multilayer applicator. The dosimetric impact of the thin copper DCC array is also assessed. Steady state fluid dynamics of the new waterbolus bag indicates nearly uniform flow with less than 1°C variation across a large (19×32cm) bolus. Thermometry data of the torso phantom acquired with computer controlled movement of fiberoptic temperature probes inside thermal mapping catheters indicate feasibility of real time feedback control for the DCC array. MR (magnetic resonance) scans of a torso phantom indicate that the waterbolus thickness across the treatment area is controlled by the pressure applied by the surrounding inflatable airbladder and applicator securing straps. The attenuation coefficient of the DCC array was measured as 3± 0.001% and 2.95±0.03 % using an ion chamber and OneDose™ dosimeters respectively. The performance of the combination applicator on patient phantoms provides valuable feedback to optimize the applicator prior use in the patient clinic.

Fast temperature optimization of multi-source hyperthermia applicators with reduced-order modeling of 'virtual sources'.

The goal of this work is to build the foundation for facilitating real-time magnetic resonance image guided patient treatment for heating systems with a large number of physical sources (e.g. antennas). Achieving this goal requires knowledge of how the temperature distribution will be affected by changing each source individually, which requires time expenditure on the order of the square of the number of sources. To reduce computation time, we propose a model reduction approach that combines a smaller number of predefined source configurations (fewer than the number of actual sources) that are most likely to heat tumor. The source configurations consist of magnitude and phase source excitation values for each actual source and may be computed from a CT scan based plan or a simplified generic model of the corresponding patient anatomy. Each pre-calculated source configuration is considered a 'virtual source'. We assume that the actual best source settings can be represented effectively as weighted combinations of the virtual sources. In the context of optimization, each source configuration is treated equivalently to one physical source. This model reduction approach is tested on a patient upper-leg tumor model (with and without temperature-dependent perfusion), heated using a 140 MHz ten-antenna cylindrical mini-annular phased array. Numerical simulations demonstrate that using only a few pre-defined source configurations can achieve temperature distributions that are comparable to those from full optimizations using all physical sources. The method yields close to optimal temperature distributions when using source configurations determined from a simplified model of the tumor, even when tumor position is erroneously assumed to be approximately 2.0 cm away from the actual position as often happens in practical clinical application of pre-treatment planning. The method also appears to be robust under conditions of changing, nonlinear, temperature-dependent perfusion. The proposed approach of using virtual sources reduces the number of variables that must be optimized to achieve a tumor-focused temperature distribution, thereby reducing the calculation time required in real-time control applications to about 1/3 to 1/4 of that required for full optimization.