Three-dimensional (3D) anatomic location, extension, and timing of severe osteoradionecrosis of the mandible.

Background: The purpose of this study was to describe the topography, extension (volume), and timing of severe osteoradionecrosis (ORN) that required mandible resection in patients previously treated for head and neck cancer at a high-volume Veterans Affairs Medical Center. Materials and methods: The records from a reference hyperbaric oxygen clinic were retrospectively analyzed (n = 50, 2018-2021). Inclusion criteria were: I) severe ORN defined as progressive ORN that required resection; II) pathologic confirmation of ORN; and III) availability of pre-operative CT-imaging. Using a radiotherapy (RT) imaging software, we performed a detailed volumetric (3D) analysis of the bone involvement by ORN. Time intervals from RT to surgery for ORN and from surgery to the last follow-up were calculated. Results: All patients that met inclusion criteria (n = 10) were male with significant smoking history (median 47.5 pack-years) and a median age of 57 years old at the time of RT. The primary tumors were: oropharynx (n = 6), oral cavity (n = 3) and nasopharynx (n = 1). The median time from RT to ORN surgery was 8 years. The most common ORN location was the posterior lateral body (molar) and six patients had associated fractures. The mean ORN volume was 3.6 cc (range: 0.6-8.3), corresponding to a mean 6.3% (range: 0.7-14) of the total mandibular volume. After a median follow-up of 13.5 months, no recurrence of ORN occurred. Three patients died of non-cancer and non-ORN-recurrence related causes (1 y OS 77.1%). Conclusion: Severe ORN occurred after a median of 8 years from the previous RT and usually affected the posterior lateral body. Surgical resection achieved excellent ORN control.

Lack of correlation between external fiducial positions and internal tumor positions during breath-hold CT.

PURPOSE: For thoracic tumors, if four-dimensional computed tomography (4DCT) is unavailable, the internal margin can be estimated by use of breath-hold (BH) CT scans acquired at end inspiration (EI) and end expiration (EE). By use of external surrogates for tumor position, BH accuracy is estimated by minimizing the difference between respiratory extrema BH and mean equivalent-phase free breathing (FB) positions. We tested the assumption that an external surrogate for BH accuracy correlates with internal tumor positional accuracy during BH CT. METHODS AND MATERIALS: In 16 lung cancer patients, 4DCT images, as well as BH CT images at EI and EE, were acquired. Absolute differences between BH and mean equivalent-phase (FB) positions were calculated for both external fiducials and gross tumor volume (GTV) centroids as metrics of external and internal BH accuracy, respectively, and the results were correlated. RESULTS: At EI, the absolute difference between mean FB and BH fiducial displacement correlated poorly with the absolute difference between FB and BH GTV centroid positions on CT images (R(2) = 0.11). Similarly, at EE, the absolute difference between mean FB and BH fiducial displacements correlated poorly with the absolute difference between FB and BH GTV centroid positions on CT images (R(2) = 0.18). CONCLUSIONS: External surrogates for tumor position are not an accurate metric of BH accuracy for lung cancer patients. This implies that care should be taken when using such an approach because an incorrect internal margin could be generated.

MRI and (1)H MRS of the breast: presence of a choline peak as malignancy marker is related to K21 value of the tumor in patients with invasive ductal carcinoma.

To assess which specific morphologic features, enhancement patterns, or pharmacokinetic parameters on breast Magnetic Resonance Imaging (MRI) could predict a false-negative outcome of Proton MR Spectroscopy ((1)H MRS) exam in patients with invasive breast cancer. Sixteen patients with invasive ductal carcinoma of the breast were prospectively included and underwent both, contrast-enhanced breast MRI and (1)H MRS examination of the breast. The MR images were reviewed and the lesions morphologic features, enhancement patterns and pharmacokinetic parameters (k21-value) were scored according to the ACR BI-RADS-MRI lexicon criteria. For the in vivo MRS studies, each spectrum was evaluated for the presence of choline based on consensus reading. Breast MRI and (1)H MRS data were compared to histopathologic findings. In vivo (1)H MRS detected a choline peak in 14/16 (88%) cancers. A false-negative (1)H MRS study occurred in 2/16 (14%) cancer patients. K21 values differed between both groups: the 14 choline positive cancers had k21 values ranging from 0.01 to 0.20/second (mean 0.083/second), whereas the two choline-negative cancers showed k21 values of 0.03 and 0.05/second, respectively (mean 0.040/second). Also enhancement kinetics did differ between both groups; typically both cancers that were choline-negative showed a late phase plateau (100%), whereas this was only shown in 5/14 (36%) of the choline positive cases. There was no difference between both groups with regard to morphologic features on MRI. This study showed that false-negative (1)H MRS examinations do occur in breast cancer patients, and that the presence of a choline peak on (1)H MRS as malignancy marker is related to the k21 value of the invasive tumor being imaged.

Comparison of breath-hold and free-breathing positions of an external fiducial by analysis of respiratory traces.

An internal target volume (ITV) accounting for respiratory-induced tumor motion is best obtained using 4DCT. However, when 4DCT is not available, inspiratory/expiratory breath-hold (BH insp, BH exp) CT images have been suggested as an alternative. In such cases, an external fiducial on the abdomen can be used as a substitute for tumor motion and CT images are acquired when the marker position matches - as judged by the therapist/physicist - its positions at previously determined free-breathing (FB) respiratory extrema (FB insp, FB exp). In this study we retrospectively determined the accuracy of these matches. Free breathing 4DCT images were acquired, followed by BH insp and BH exp CT images for 25 patients with non-small-cell lung cancer. Respiration was monitored using a commercial external fiducial system, which generates positional information while CT studies are conducted. Software was written for statistically analyzing the displacement of the external fiducial during BH insp and BH exp CT acquisition and comparing these displacements with corresponding mean FB extrema positions (FB insp and FB exp, respectively) using a Student's t-test. In 72% of patients, mean positions at BH insp differed significantly from mean positions at FB insp (p < 0.05: 0.13 - 1.40 cm). In 92% of patients, mean positions at BH exp differed significantly from mean positions at FB exp (p < 0.05: 0.03 - 0.70 cm), although this difference was smaller than 0.5 cm in many cases (median = 0.34 cm). Our findings indicate that relying solely on abdominal external markers for accurate BH CT imaging in order to accurately estimate FB extrema positions may be subject to significant error.

Assessing respiration-induced tumor motion and internal target volume using four-dimensional computed tomography for radiotherapy of lung cancer.

PURPOSE: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. METHODS AND MATERIALS: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. RESULTS: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. CONCLUSIONS: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung.

Tumor oximetry: comparison of 19F MR EPI and electrodes.

We recently described a novel approach to measuring regional tumor oxygen tension. This approach is based on 19F pulse burst saturation recovery NMR echo planar imaging relaxometry of hexafluorobenzene or "FREDOM" (Fluorocarbon Relaxometry using Echo planar imaging for Dynamic Oxygen Mapping). We have now compared oxygen tension measurements using FREDOM with a traditional polarographic method (the Eppendorf Histograph) in a group of size matched Dunning prostate rat tumors R3327-AT1. We also compare MR and electrode approaches to monitoring dynamic changes with respect to interventions and demonstrate extension of the MR technique to rat breast tumors.

Quality assurance of magnetic resonance spectroscopic imaging-derived metabolic data.

PURPOSE: Spatially resolved metabolite maps, as measured by magnetic resonance spectroscopic imaging (MRSI) methods, are being increasingly used to acquire metabolic information to guide therapy, with metabolite ratio maps perhaps providing the most diagnostic information. We present a quality assurance procedure for MRSI-derived metabolic data acquired ultimately for guiding conformal radiotherapy. METHODS AND MATERIALS: An MRSI phantom filled with brain-mimicking solutions was custom-built with an insert holding eight vials containing calibration solutions of precisely varying metabolite concentrations that emulated increasing grade/density of brain tumor. Phantom metabolite ratios calculated from fully relaxed 1D, 2D, and 3D MRS data for each vial were compared with calibrated metabolite ratios acquired at 9.4 T. Additionally, 3D ratio maps were "discretized" to eight pseudoabnormality levels on a slice-by-slice basis and the accuracy of this procedure was verified. RESULTS: Regression analysis revealed expected linear relationships between experimental and calibration metabolite ratios with intercepts close to zero for the three acquisition modes. 1D MRS data agreed most with theoretical considerations (regression coefficient, b = 0.969; intercept 0.008). The 2D (b = 1.049; intercept -0.199) and 3D (correlation coefficient r(2) = 0.9978-0.7336 for five slices) MRSI indicated reduced MRS data quality in regions of degraded B(0) and B(1) homogeneity. Pseudoabnormality levels were found to be consistent with expectations within regions of adequate B(0) homogeneity. CONCLUSIONS: This simple phantom-based approach to generate baseline calibration curves for all MRS acquisition modes may be useful to identify temporal deviations from acceptable data quality in a routine clinical environment or for testing new MRS and MRSI acquisition software.

Inverse planning for functional image-guided intensity-modulated radiation therapy.

Radiation therapy is an image-guided process whose success critically depends on the imaging modality used for treatment planning and the level of integration of the available imaging information. In this work, we establish a dose optimization framework for incorporating metabolic information from functional imaging modalities into the intensity-modulated radiation therapy (IMRT) inverse planning process and to demonstrate the technical feasibility of planning deliberately non-uniform dose distributions in accordance with functional imaging data. For this purpose, a metabolic map from functional images is discretized into a number of abnormality levels (ALs) and then fused with CT images. To escalate dose to the metabolically abnormal regions, we assume, for a given spatial point, a linear relation between the AL and the prescribed dose. But the formalism developed here is independent of the assumption and any other relation between AL and prescription is applicable. For a given AL and prescription relation, it is only necessary to prescribe the dose to the lowest AL in the target and the desired doses to other regions with higher AL values are scaled accordingly. To accomplish differential sparing of a sensitive structure when its functional importance (FI) distribution is known, we individualize the tolerance doses of the voxels within the structure according to their Fl levels. An iterative inverse planning algorithm in voxel domain is used to optimize the system with in homogeneous dose prescription. To model intra-structural trade-off, a mechanism is introduced through the use of voxel-dependent weighting factors, in addition to the conventional structure specific weighting factors which model the inter-structural trade-off. The system is used to plan a phantom case with a few hypothetical functional distributions and a brain tumour treatment with incorporation of magnetic resonance spectroscopic imaging data. The results indicated that it is technically feasible to produce deliberately non-uniform dose distributions according to the functional imaging requirements. Integration of functional imaging information into radiation therapy dose optimization allows for consideration of patient-specific biologic information and provides a significant opportunity to truly individualize radiation treatment. This should enhance our capability to safely and intelligently escalate dose and lays the technical foundation for future clinical studies of the efficacy of functional imaging-guided IMRT.