Dee H. Wu

Longitudinal Changes in Tumor Perfusion Pattern during the Radiation Therapy Course and its Clinical Impact in Cervical Cancer

PURPOSE To study the temporal changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns during the radiation therapy (RT) course and their influence on local control and survival in cervical cancer. METHODS AND MATERIALS DCE-MRI was performed in 98 patients with Stage IB(2)-IVA cervical cancer before RT (pre-RT) and during early RT (20-25 Gy) and mid-RT (45-50 Gy). Signal intensity (SI) from the DCE-MRI time-SI curve was derived for each tumor voxel. The poorly perfused low-DCE tumor subregions were quantified as lower 10th percentiles of SI (SI10). Local control, disease-specific survival, and overall survival were correlated with DCE parameters at pre-RT, early RT, and mid-RT. Median follow-up was 4.9 (range, 0.2-9.0) years. RESULTS Patients (16/98) with initial pre-RT high DCE (SI10 >or=2.1) had 100% 5-year local control, 81% disease-specific survival, and 81% overall survival, compared with only 79%, 61%, and 55%, respectively, in patients with pre-RT low DCE. Conversion from pre-RT low DCE to high DCE in early RT (28/82 patients) was associated with higher local control, disease-specific survival, and overall survival (93%, 74%, and 67%, respectively). In comparison with all other groups, outcome was worst in patients with persistently low DCE from pre-RT throughout the mid-RT phase (66%, 44%, and 43%; p = 0.003, 0.003, and 0.020; respectively). CONCLUSION Longitudinal tumor perfusion changes during RT correlate with treatment outcome. Persistently low perfusion in pre-RT, early RT, and mid-RT indicates a high risk of treatment failure, whereas outcome is favorable in patients with initially high perfusion or subsequent improvements of initially low perfusion. These findings likely reflect reoxygenation and may have potential for noninvasive monitoring of intra-treatment radio-responsiveness and for guiding adaptive therapy.

Serial therapy-induced changes in tumor shape in cervical cancer and their impact on assessing tumor volume and treatment response

OBJECTIVE The purpose of this study was to evaluate the patterns and distribution of tumor shape and its temporal change during radiation therapy (RT) in cervical cancer and the effect of tumor configuration changes on the correlation between region of interest (ROI)-based and diameter-based MRI tumor measurement. MATERIALS AND METHODS Serial MRI examinations (T1-weighted and T2-weighted images) were performed in 60 patients (age range, 29-75 years; mean, 53.3 years) with advanced cervical cancer (stages IB2-IVB/recurrent) who were treated with RT at four time points: start of RT, during RT (at 2-2.5 and at 4-5 weeks of RT), and post-RT. Tumor configuration was classified qualitatively into oval, lobulated, and complex based on MR film review. Two methods of tumor volume measurement were compared: ellipsoid computation of three orthogonal diameters (diameter based) and ROI volumetry by delineating the entire tumor volume on the MR workstation (ROI based). Temporal changes of tumor shape and the respective tumor volumes measured by the two methods were analyzed using linear regression analysis. RESULTS Most tumors (70%) had a non-oval (lobulated and complex) shape before RT and became increasingly irregular during and after RT: 84% at 2-2.5 weeks of RT (p = 0.037), 86% (p = 0.025) at 4-5 weeks, and 96% post-RT (p = 0.010), compared with 70% pre-RT. Diameter-based and ROI-based measurement correlated well before RT (r = 0.89) but not during RT (r = 0.68 at 2-2.5 weeks, r = 0.67 at 4-5 weeks of RT). CONCLUSION Most cervical cancers are not oval in shape pretherapy, and they become increasingly irregular during and after therapy because of nonconcentric tumor shrinkage. ROI-based volumetry, which can optimally measure irregular volumes, may provide better response assessment during treatment than diameter-based measurement.

Interobserver variation in cervical cancer tumor delineation for image-based radiotherapy planning among and within different specialties.

Radiation therapy for cervical cancer involves a team of specialists, including diagnostic radiologists (DRs), radiation oncologists (ROs), and medical physicists (MPs), to optimize imaging‐based radiation therapy planning. The purpose of the study was to investigate the interobserver variations in tumor delineation on MR images of cervical cancer within the same and among different specialties. Twenty MRI cervical cancer studies were independently reviewed by two DRs, two ROs, and two MPs. For every study, each specialist contoured the tumor regions of interest (ROIs) on T2‐weighted Turbo Spin Echo sagittal images on all slices containing tumor, and the total tumor volume was computed for statistical analysis. Analysis of variance (ANOVA) was used to compare the differences in tumor volume delineation among the observers. A graph of all tumor‐delineated volumes was generated, and differences between the maximum and minimum volumes over all the readers for each patient dataset were computed. Challenges during the evaluation process for tumor delineation were recorded for each specialist. Interobserver variations of delineated tumor volumes were significant (p<0.01) among all observers based on a repeated measures ANOVA, which produced an F(5,95)=3.55. The median difference between the maximum delineated volume and minimum delineated volume was 33.5 cm3 (which can be approximated by a sphere of 4.0 cm diameter) across all 20 patients. Challenges noted for tumor delineation included the following: (1) partial voluming by parametrial fat at the periphery of the uterus; (2) extension of the tumor into parametrial space; (3) similar signal intensity of structures proximal to the tumor such as ovaries, muscles, bladder wall, bowel loops, and pubic symphysis; (4) postradiation changes such as heterogeneity and necrosis; (5) susceptibility artifacts from bowels and vaginal tampons; (6) presence of other pathologies such as atypical myoma; (7) factors that affect pelvic anatomy, including the degree of bladder distension, bowel interposition, uterine malposition, retroversion, and descensus. Our limited study indicates significant interobserver variation in tumor delineation. Despite rapid progress in technology, which has improved the resolution and precision of image acquisition and the delivery of radiotherapy to the millimeter level, such “human” variations (at the centimeter level) may overshadow the gain from technical advancement and impact treatment planning. Strategies of standardization and training in tumor delineation need to be developed. PACS number(s):

A method for safely resecting anterior butterfly gliomas: the surgical anatomy of the default mode network and the relevance of its preservation

OBJECTIVE Gliomas invading the anterior corpus callosum are commonly deemed unresectable due to an unacceptable risk/benefit ratio, including the risk of abulia. In this study, the authors investigated the anatomy of the cingulum and its connectivity within the default mode network (DMN). A technique is described involving awake subcortical mapping with higher attention tasks to preserve the cingulum and reduce the incidence of postoperative abulia for patients with so-called butterfly gliomas. METHODS The authors reviewed clinical data on all patients undergoing glioma surgery performed by the senior author during a 4-year period at the University of Oklahoma Health Sciences Center. Forty patients were identified who underwent surgery for butterfly gliomas. Each patient was designated as having undergone surgery either with or without the use of awake subcortical mapping and preservation of the cingulum. Data recorded on these patients included the incidence of abulia/akinetic mutism. In the context of the study findings, the authors conducted a detailed anatomical study of the cingulum and its role within the DMN using postmortem fiber tract dissections of 10 cerebral hemispheres and in vivo diffusion tractography of 10 healthy subjects. RESULTS Forty patients with butterfly gliomas were treated, 25 (62%) with standard surgical methods and 15 (38%) with awake subcortical mapping and preservation of the cingulum. One patient (1/15, 7%) experienced postoperative abulia following surgery with the cingulum-sparing technique. Greater than 90% resection was achieved in 13/15 (87%) of these patients. CONCLUSIONS This study presents evidence that anterior butterfly gliomas can be safely removed using a novel, attention-task based, awake brain surgery technique that focuses on preserving the anatomical connectivity of the cingulum and relevant aspects of the cingulate gyrus.

Improvement to functional Magnetic Resonance Imaging (fMRI) Methods using Non-rigid Body Image Registration Methods for Correction in the Presence of Susceptibility Artifact Effects

Subject head movement, during the experimental and/or clinical procedure is an inevitable part of the functional magnetic resonance imaging (fMRI) brain mapping methods despite the availability of a large variety of head fixation devices employed in these studies. Thus, image registration is an essential processing step in fMRI. This is due to the fact that there is inevitable movement during the course on an fMRI experiment. An additional challenge is the explicit geometrical deformations associated with MRI. It is known that orientational changes are problematic in MRI in the presence of susceptibility differences especially between bone-tissue and air-tissue interfaces. This paper presents two registration strategies for fMRI registration, one using rigid registration based on maximization of mutual information, and the second is non-rigid registration adapted from Thirions demons algorithm to demonstrate the importance and impact on fMRI in regions of susceptibility and its dependence on the image registration methodology

White matter connections of the inferior parietal lobule: A study of surgical anatomy

Interest in the function of the inferior parietal lobule (IPL) has resulted in increased understanding of its involvement in visuospatial and cognitive functioning, and its role in semantic networks. A basic understanding of the nuanced white‐matter anatomy in this region may be useful in improving outcomes when operating in this region of the brain. We sought to derive the surgical relationship between the IPL and underlying major white‐matter bundles by characterizing macroscopic connectivity.

368 Anatomy and White Matter Connections of the Orbitofrontal Gyrus.

INTRODUCTION The orbitofrontal cortex is understood to have a role in outcome evaluation and risk assessment, and is commonly involved by infiltrative tumors. A detailed understanding of the exact location and nature of associated white tracts could go far to prevent postoperative morbidity related to declining capacity. Through diffusion tensor imaging (DTI)-based fiber tracking validated by gross anatomical dissection as ground truth, we have characterized these connections based on relationships to other well-known structures. METHODS Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. We evaluated the orbitofrontal cortex as a whole based on connectivity with other regions. All orbitofrontal cortex tracts were mapped in both hemispheres, and lateralization index was calculated with resultant tract volumes. Ten postmortem dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts. RESULTS We identified 3 major connections of the orbitofrontal cortex: a bundle to the thalamus and anterior cingulate gyrus passing inferior to the caudate and medial to the vertical fibers of the thalamic projections; a bundle to the brainstem traveling lateral to the caudate and medial to the internal capsule; and radiations to the parietal and occipital lobes traveling with the inferior fronto-occipital fasciculus. There was no significant lateralization for any of the tracts described. CONCLUSION The orbitofrontal cortex is an important center for processing visual, spatial, and emotional information. Subtle differences in executive functioning following surgery for frontal lobe tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study.

Transient stenotic-like occlusions as a possible mechanism for renovascular hypertension due to aneurysm

The pathophysiologic basis of hypertension secondary to a renal artery aneurysm has not been established. Changes in renal artery geometry and resultant hemodynamic alterations activate the renin-angiotensin-aldosterone system and lead to hypertension. Hemodynamic pressure losses created by blood flowing through an abnormally structured renal artery with an aneurysm predictably would provoke a similar circumstance. The present study provides a hemodynamic rationale for this hypothesis. Using computational fluid dynamics, we have modeled renal flow for selected aneurysmal geometries. These studies reveal that pressure loss across the renal artery does not change ( approximately 0.9 mm Hg) significantly when a nondeformable aneurysm is interposed on the system. The calculations, however, demonstrate that the pressure on the aneurysm walls supports the presence of forces deforming and thereby obstructing the renal artery. A deformed wall was assumed and various degrees of occlusion were modeled. A partial occlusion of 60% resulted in a renal artery pressure loss of approximately 10 mm Hg. These simulations, when applied to aneurysms at various locations on the renal artery and with various degrees of occlusion, consistently resulted in pathologically relevant pressure losses. These findings lead to a new hypothesis of how aneurysms are associated with renovascular hypertension.

Anatomy and white matter connections of the orbitofrontal gyrus

OBJECTIVE The orbitofrontal cortex (OFC) is understood to have a role in outcome evaluation and risk assessment and is commonly involved with infiltrative tumors. A detailed understanding of the exact location and nature of associated white matter tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging-based fiber tracking validated by gross anatomical dissection as ground truth, the authors have characterized these connections based on relationships to other well-known structures. METHODS Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. The OFC was evaluated as a whole based on connectivity with other regions. All OFC tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes. Ten postmortem dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts. RESULTS The authors identified 3 major connections of the OFC: a bundle to the thalamus and anterior cingulate gyrus, passing inferior to the caudate and medial to the vertical fibers of the thalamic projections; a bundle to the brainstem, traveling lateral to the caudate and medial to the internal capsule; and radiations to the parietal and occipital lobes traveling with the inferior fronto-occipital fasciculus. CONCLUSIONS The OFC is an important center for processing visual, spatial, and emotional information. Subtle differences in executive functioning following surgery for frontal lobe tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study.

Dynamic Contrast-Enhanced MR Imaging for Predicting Tumor Control in Patients with Cervical Cancer

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