K Ahn

Dosimetric comparison of bone marrow-sparing intensity-modulated radiotherapy versus conventional techniques for treatment of cervical cancer.

PURPOSE To compare bone marrow-sparing intensity-modulated pelvic radiotherapy (BMS-IMRT) with conventional (four-field box and anteroposterior-posteroanterior [AP-PA]) techniques in the treatment of cervical cancer. METHODS AND MATERIALS The data from 7 cervical cancer patients treated with concurrent chemotherapy and IMRT without BMS were analyzed and compared with data using four-field box and AP-PA techniques. All plans were normalized to cover the planning target volume with the 99% isodose line. The clinical target volume consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprised the lumbosacral spine and ilium and the ischium, pubis, and proximal femora (lower pelvis bone marrow). Dose-volume histograms for the planning target volume and normal tissues were compared for BMS-IMRT vs. four-field box and AP-PA plans. RESULTS BMS-IMRT was superior to the four-field box technique in reducing the dose to the PBM, small bowel, rectum, and bladder. Compared with AP-PA plans, BMS-IMRT reduced the PBM volume receiving a dose >16.4 Gy. BMS-IMRT reduced the volume of ilium, lower pelvis bone marrow, and bowel receiving a dose >27.7, >18.7, and >21.1 Gy, respectively, but increased dose below these thresholds compared with the AP-PA plans. BMS-IMRT reduced the volume of lumbosacral spine bone marrow, rectum, small bowel, and bladder at all dose levels in all 7 patients. CONCLUSION BMS-IMRT reduced irradiation of PBM compared with the four-field box technique. Compared with the AP-PA technique, BMS-IMRT reduced lumbosacral spine bone marrow irradiation and reduced the volume of PBM irradiated to high doses. Therefore BMS-IMRT might reduce acute hematologic toxicity compared with conventional techniques.

MRI Guidance for Accelerated Partial Breast Irradiation in Prone Position: Imaging Protocol Design and Evaluation

PURPOSE To design and evaluate a magnetic resonance imaging (MRI) protocol to be incorporated in the simulation process for external beam accelerated partial breast irradiation. METHODS AND MATERIALS An imaging protocol was developed based on an existing breast MRI technique with the patient in the prone position on a dedicated coil. Pulse sequences were customized to exploit T1 and T2 contrast mechanisms characteristic of lumpectomy cavities. A three-dimensional image warping algorithm was included to correct for geometric distortions related to nonlinearity of spatially encoding gradients. Respiratory motion, image distortions, and susceptibility artifacts of 3.5-mm titanium surgical clips were examined. Magnetic resonance images of volunteers were acquired repeatedly to analyze residual setup deviations resulting from breast tissue deformation. RESULTS The customized sequences generated high-resolution magnetic resonance images emphasizing lumpectomy cavity morphology. Respiratory motion was negligible with the subject in the prone position. The gradient-induced nonlinearity was reduced to less than 1 mm in a region 15 cm away from the isocenter of the magnet. Signal-void regions of surgical clips were 4 mm and 8 mm for spin echo and gradient echo images, respectively. Typical residual repositioning errors resulting from breast deformation were estimated to be 3 mm or less. CONCLUSIONS MRI guidance for accelerated partial breast irradiation with the patient in the prone position with adequate contrast, spatial fidelity, and resolution is possible.

Multiparametric imaging of tumor oxygenation, redox status, and anatomical structure using Overhauser-enhanced MRI-prepolarized MRI system.

An integrated Overhauser‐enhanced MRI–Prepolarized MRI system was developed to obtain radiobiological information that could be accurately coregistered with diagnostic quality anatomic images. EPR and NMR images were acquired through the double resonance technique and field cycling of the main magnetic field from 5 mT to 0.5 T. Dedicated EPR and NMR coils were devised to minimize radiofrequency power deposition with high signal‐to‐noise ratio. Trityl and nitroxide radicals were used to characterize oxygen and redox sensitivities of multispin echo Overhauser‐enhanced MRI. Oxygen resolution of 3 mmHg was obtained from 2 mM deoxygenated trityl phantoms. Trityl radicals were stable in reducing environments and did not alter the redox‐sensitive decaying rate of the nitroxide signals. Nitroxide radicals had a compounding effect for the trityl oximetry. Tumor oxygenation and redox status were acquired with anatomical images by injecting trityl and nitroxide probes subsequently in murine tumors. The Overhauser‐enhanced MRI–Prepolarized MRI system is ready for quantitative longitudinal imaging studies of tumor hypoxia and redox status as radiotherapy prognostic factors. Magn Reson Med, 2011.

TU-E-214-02: Overhauser Oxygenation Imaging: Physics, Instrumentation and Pre-Clinical Applications

Tumor oxygenation and redox status are important determinants of the malignant behavior of cancers and their response to radiation therapy. Concentration of molecular oxygen is directly related to the generation of non‐restorable DNA damage. Tissueredox status indicates catalytic cellular activities to scavenge free radicals that initiate a chain of events for DNA damage by an ionizing radiation. Thus a non‐invasive system that obtains this information on relevant time scales with anatomical context could facilitate longitudinal studies of the multi‐faceted tumor environment. Changes in the resonant properties of exogenous narrow‐line electron spin (free radical) probes in presence of oxygen can be sensed by electron paramagnetic resonance as well as Overhauser‐enhanced magnetic resonance (OMR). In OMR, the dipolar interaction between protons and the unpaired electron of the spin probe results in strong increase of the protonMR signal. The enhancement depends on several factors such as spin probe and oxygen concentration, longitudinal relaxation times, and the magnitude of the radiofrequency magnetic field that manipulates the electron spins. Specific imaging sequences decoupling these factors in spatially encoded manner can generate quantitative spatial maps not only of tumor oxygenation but also micro‐vascular parameters. Furthermore, these physiological maps can be natively fused with anatomical MRimages generated with the same hardware in the same imaging session. This information can be acquired repeatedly for quantitative longitudinal imaging experiments to explore both oxygenation and redox status in small animals as prognostic factors for radiation therapy. Learning objectives: 1. Understand the basic physics behind the Overhauser enhancement and enumerate the factors that determine its magnitude. 2. Recognize the main hardware components of an Overhauser oxygenation imager and understand the operating parameters of the imaging system in contrast to these of high‐field diagnostic MR scanner. 3. Understand a typical OMR imaging sequence and subsequent image analysis to derive oxygenation maps. 4. Understand typical OMRI applications in cancer‐related studies.

TH‐D‐201C‐01: Advancing an Integrated Overhauser‐Enhanced MRI (OMRI) ‐ Prepolarized MM (PMRI) System Toward Quantitative Longitudinal Studies of Tumor Hypoxia and Redox Status

Purpose: To advance the imaging performance of an integrated Overhauser‐enhanced MRI (OMRI) ‐ prepolarized MRI (PMRI) system to enable quantitative longitudinal imaging studies of multi‐faceted tumor environment by using both electron paramagnetic resonance(EPR) and nuclear magnetic resonance(NMR)Method and Materials: A field‐cycled OMRI‐PMRI system was further developed to achieve the sensitivity that identifies radiobiological hypoxia and redox status. A dedicated 5‐cm saddle coil delivered 154‐MHz EPR radiofrequency (RF) pulses to induce the Overhauser effect with a high EPR B1 efficiency. A 3‐cm 5.5‐MHz NMR Litz‐wire saddle coil concentric to the EPR coil achieved high signal‐to‐noise ratio with an efficient filling factor. B0 was at 5 mT 0.13 T 0.5 T for EPR irradiation NMR readout NMR prepolarization respectively. Gradient echo and multi‐spin echo pulse sequences were implemented using a custom MRI console to acquire images with minimal phase distortion. Trityl phantoms were prepared under normoxic and anoxic environment for pO2calibration. Various amounts of ascorbic acid (AsA) were injected to the mixtures of trityl and nitroxide (3‐carbamoyl PROXYL) phantoms to characterize the redox sensitivity. Results: Oxygen resolution of 4.1 torr and 3.5 torr were obtained from 4‐min double power (0.3 32 W) spin‐echo OMRI (TR/TE 1600/30 ms) for pure deoxygenated 1‐mM and 2‐mM trityl phantoms. Trityl radicals were not reduced by AsA and did not alter the reduction decay rate of the nitroxides (−0.07/min −0.13/min for 5 10‐mM AsA). Saturation factor measurements at various EPR RF power levels indicated a feasibility of accurate pO2calibration for the mixtures of trityl and nitroxide radicals. Conclusion: Our OMRI‐PMRI system is capable of multi‐parametric imaging sensitive to pO2redox status proton T1 and T2. The imager is ready to acquire physiological information in small animals accurately co‐registered with diagnostic quality anatomic NMRimages.

TH‐D‐304A‐01: Development of Multi‐Parametric Molecular Imager by Integrating Overhauser‐Enhanced MRI (OMRI) with Prepolarized MRI (PMRI)

Purpose: To develop a multi‐parametric molecular imager to assess tumor hypoxia and redox status by integrating Overhauser‐enhanced MRI (OMRI) with prepolarized MRI (PMRI). Method and Materials: PMRI system acquires anatomic MR images comparable to conventional MRI. With a moderate hardware augmentation of the PMRI, we implemented field‐cycled OMRI and obtained electron paramagnetic resonance(EPR)images of nitroxide spin probes. Phantoms were made of 2‐cc tubes filled with pure water, <5‐mM solutions of 3‐carbamoyl‐PROXYL. A custom MRI console was used to insert 25‐W EPR radiofrequency (RF) pulses that enhanced NMR signal of the coupled water protons. A saddle coil (3.5 cm diameter, 2.5 cm length) tuned to 186 MHz was used as the EPR irradiator. To elicit the Overhauser effect, each NMR RF pulse (2.23 MHz) was preceded by the EPR RF pulse during a low field‐cycled interval. Free induction decay (FID) was observed at the EPR B0 swept from 4.2 mT to 9.5 mT. For OMRI, the low‐field cycle was fixed at 4.8 mT to exploit the low‐frequency hyperfine peak of the nitroxide. Generic gradient‐echo 0.05‐T MR images were obtained with either prepolarization or Overhauser enhancement. Results: FID acquisition of a 2.5‐mM nitroxide phantom identified three hyperfine lines of 14 N at 4.8, 6.2 and 8.1 mT. Each peak represented an enhancement factor of 13 with 300‐ms EPR RF pulse. Increasing enhancements were observed with longer durations of EPR irradiation, which indicated 0.71‐s T1 of the phantom. We observed similar intensities of water and <5‐mM nitroxide solutions from 0.15‐T PMRI. The OMRI showed characteristic EPR intensities and clearly separated the 2.5‐mM and 5‐mM nitroxide phantoms from the water phantom. Conclusion: The integrated OMRI‐PMRI system demonstrated sensitivity to both EPR and NMR. The imager can potentially acquire physiological information in small animals accurately co‐registered with high‐quality anatomic NMRimages.

SU‐GG‐T‐71: Dosimetric Comparison of Bone Marrow‐Sparing Intensity Modulated Radiation Theraphy Versus Conventional Techniques for the Treatment of Cervical Cancer

Purpose: To compare bone marrow‐sparing intensity modulated pelvic radiation therapy (BMS‐IMRT) to conventional (AP/PA and 4‐field box) techniques in the treatment of cervical cancer.Method and Materials: Seven cervical cancer patients treated with concurrent chemotherapy and IMRT were analyzed. We compared BMS‐IMRT to AP/PA and 4‐field box plans. All plans were normalized to cover PTV with the 99% isodose line. The clinical target volume (CTV) consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. A 1.0 cm uniform margin was added to create the PTV. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprised the lumbosacral spine (LSBM), ilium (IBM), and ischium, pubis, and proximal femora (lower pelvis bone marrow — LPBM). Dose volume histograms for PTV and normal tissues were compared for BMS‐IMRT vs. 4‐field box and AP/PA plans. Results: BMS‐IMRT was superior to 4‐field box in reducing the dose to PBM, small bowel, rectum and bladder. Compared to AP/PA, BMS‐IMRT reduced the PBM volume receiving a dose above 16.4 Gy, however, that receiving below this threshold dose was increased. BMS‐IMRT reduced IBM, LPBM and bowel radiation above 27.7 Gy, 18.7 Gy, and 21.1 Gy, respectively, but increased dose below these thresholds, compared to AP/PA plans. BMS‐IMRT reduced the volume of LSBM, rectum, small bowel, and bladder at all dose levels in all 7 patients. Conclusion: BMS‐IMRT reduced irradiation of PBM compared to 4‐field box techniques. Compared to AP/PA, BMS‐IMRT reduced LSBM irradiation and reduced the volume of PBM irradiated to high doses, but increased that irradiated to low doses. BMS‐IMRT may reduce acute HT compared to conventional techniques.

SU‐DD‐A1‐05: Treatment Planning of Prone Position Accelerated Partial Breast Irradiation Customized for Magnetic Resonance Imaging Guidance

Purpose: It is important to deliver an optimized dose distribution to an accurately delineated target volume for a successful accelerated partial breast irradiation (APBI) treatment. Breast magnetic resonance imaging(MRI) could improve lumpectomy delineation. We investigated treatment plans for CyberKnife and conventional C‐arm LINAC delivery of MRI‐guided APBI in prone position. Method and Materials: We acquired a CT scan of a patient positioned on a mechanical assembly with the same geometry as the dedicated MR coil to simulate the position during breast MRI acquisition. Ellipsoidal virtual PTVs of 4 cm were defined in the anterior part and in the lower outer quadrant of the right breast. Treatment plans were generated by inverse planning techniques for each system. For CyberKnife, we minimized beam directions from posterior to anterior to protect critical normal tissues(heart,lung and contralateral breast) and normalized the maximum dose to 120% of the prescription dose (38.5 Gy). For the conventional LINAC, we excluded any beams directed towards the critical normal tissues and normalized the plan to achieve 99% of the prescription coverage for 99% of PTV. Results: LINAC‐based plans resulted in maximum doses of 41.6 Gy in PTV and ⩽ 0.5 Gy in the critical normal structures. CyberKnife‐based plans led to 90% of the prescription dose coverage for 95% of PTV. Maximum doses were ⩽ 0.5 Gy in contralateral breast, ⩽ 1.9 Gy in heart, and ⩽ 4.2 Gy in both lungs. The fraction of normal ipsilateral breast tissue receiving ⩾ 37 Gy was 1% and 5% for CyberKnife and LINAC plans respectively. Conclusion: CyberKnife and LINAC generate treatment plans for MRI‐guided prone position APBI with acceptable dose distributions. The standard LINAC requires careful beam configuration to secure clearances between equipments. CyberKnife results in better conformity and slightly higher doses in the critical normal tissues.

TU‐C‐351‐01: Design of Magnetic Resonance Imaging Protocol for Accelerated Partial Breast Irradiation in Prone Position

Purpose: Accurate delineation of tumor bed is prerequisite for an effective treatment of breast cancer with accelerated partial breast irradiation (APBI) technique. Magnetic resonance imaging(MRI) has high contrast mechanisms that could enable precise contouring of the lumpectomy cavity. We investigated practical issues pertinent to MR‐guided breast radiation therapy using customized pulse sequences. Method and Materials: Unilateral breast MRimages were obtained from two healthy volunteers in prone position on a dedicated coil. Radiation therapists positioned the volunteers in reproducible setup using a waterproof marker. We acquired 6‐min 3D MRimages to analyze setup uncertainty and fast 2D MRimages of 0.5‐s temporal resolution to detect respiratory motion. An accurate 3D warping‐correction algorithm was evaluated and used to restore spatial fidelity from geometric distortions due to MR gradient non‐linearities. MRimages of surgical clips as fiducial were obtained using pulse sequences designed to provide high signal from lumpectomy cavity. Results: Average breathing motion in the breast was found to be less than 0.5 mm in prone position. Setup deviations of 1 cm were observed between series of intended prone positioning. Rigid image registration based on local anatomy structure resulted in a residual error which was up to 5 mm at the peripheral region of the breast. Gradient‐induced non‐linearity led to 1 cm distortion in the uncorrected phantom image at the region 15 cm away from the main magnet axis. The 3D correction algorithm reduced the deviation to < 1 mm. We observed 4 mm signal void artifacts of surgical clips. Conclusion: We obtained MRimages of suitable quality from volunteers using pulse sequences customized for lumpectomy site identification. MR‐guided APBI in prone position would require 5 mm uniform expansion of clinical target volume with the employment of an appropriate on‐board imaging technique.