Comparison of computed tomography shielding design methods using RadShield.

PURPOSE: To comprehensively compare four computed tomography (CT) scanner shielding design methods using RadShield, a Java-based graphical user interface (GUI). METHODS: RadShield, a floor plan based GUI, was extended to calculate air kerma and barrier thickness using accepted methods from the National Council on Radiation Protection and Measurements (NCRP), the British Institute of Radiology, and a method using isodose maps, for spatially distributed points beyond user defined barriers. For a stationary CT scanner, the overall shielding recommendations found using RadShield were also compared to those found by American Board of Radiology certified diagnostic medical physicists using the conventional NCRP dose length product method and the isodose map method. RESULTS: The results between methods differed significantly for calculation point locations beyond the gantry and to the rear of the gantry. Overall shielding design recommendations across the four methods yielded similar average air kerma and thickness values for the barriers. CONCLUSIONS: RadShield was extended to perform CT shielding design and proved reliable using four methods.

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PURPOSE: Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. MATERIALS AND METHODS: Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. RESULTS: Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. CONCLUSIONS: Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy.

RadShield: semiautomated shielding design using a floor plan driven graphical user interface.

The purpose of this study was to introduce and describe the development of RadShield, a Java-based graphical user interface (GUI), which provides a base design that uniquely performs thorough, spatially distributed calculations at many points and reports the maximum air-kerma rate and barrier thickness for each barrier pursuant to NCRP Report 147 methodology. Semiautomated shielding design calculations are validated by two approaches: a geometry-based approach and a manual approach. A series of geometry-based equations were derived giv-ing the maximum air-kerma rate magnitude and location through a first derivative root finding approach. The second approach consisted of comparing RadShield results with those found by manual shielding design by an American Board of Radiology (ABR)-certified medical physicist for two clinical room situations: two adjacent catheterization labs, and a radiographic and fluoroscopic (R&F) exam room. RadShield's efficacy in finding the maximum air-kerma rate was compared against the geometry-based approach and the overall shielding recommendations by RadShield were compared against the medical physicist's shielding results. Percentage errors between the geometry-based approach and RadShield's approach in finding the magnitude and location of the maximum air-kerma rate was within 0.00124% and 14 mm. RadShield's barrier thickness calculations were found to be within 0.156 mm lead (Pb) and 0.150 mm lead (Pb) for the adjacent catheteriza-tion labs and R&F room examples, respectively. However, within the R&F room example, differences in locating the most sensitive calculation point on the floor plan for one of the barriers was not considered in the medical physicist's calculation and was revealed by the RadShield calculations. RadShield is shown to accurately find the maximum values of air-kerma rate and barrier thickness using NCRP Report 147 methodology. Visual inspection alone of the 2D X-ray exam distribution by a medical physicist may not be sufficient to accurately select the point of maximum air-kerma rate or barrier thickness.

Sex difference in brain functional connectivity of hippocampus in Alzheimer's disease.

Alzheimer's disease (AD), affecting nearly 6.5 million people, is the fifth leading cause of death in individuals 65 years or older in the USA. Prior research has shown that AD disproportionality affects females; females have a greater incidence rate, perform worse on a variety of neuropsychological tasks, and have greater total brain atrophy. Recent research has linked these sex differences to neuroimaging markers of brain pathology, such as hippocampal volumes. Specifically, research from our lab found that functional connectivity from the hippocampus to the precuneus cortex and brain stem was significantly stronger in males than in females with mild cognitive impairment. The aim of this study was to extend our understanding to individuals with AD and to determine if these potential sex-specific functional connectivity biomarkers extend through different disease stages. The resting state fMRI and T2 MRI of cognitively normal individuals (n = 32, female = 16) and individuals with AD (n = 32, female = 16) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed using the Functional Connectivity Toolbox (CONN). Our results demonstrate that males had a significantly stronger interhemispheric functional connectivity between the left and right hippocampus compared to females. These results improve our current understanding of the role of the hippocampus in sex differences in AD. Understanding the contribution of impaired functional connectivity sex differences may aid in the development of sex-specific precision medicine for improved AD treatment.

Sex differences in brain functional connectivity of hippocampus in mild cognitive impairment.

Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer's Disease (AD). Prior research shows that females are more impacted by MCI than males. On average females have a greater incidence rate of any dementia and current evidence suggests that they suffer greater cognitive deterioration than males in the same disease stage. Recent research has linked these sex differences to neuroimaging markers of brain pathology, such as hippocampal volumes. Specifically, the rate of hippocampal atrophy affects the progression of AD in females more than males. This study was designed to extend our understanding of the sex-related differences in the brain of participants with MCI. Specifically, we investigated the difference in the hippocampal connectivity to different areas of the brain. The Resting State fMRI and T2 MRI of cognitively normal individuals (n = 40, female = 20) and individuals with MCI (n = 40, female = 20) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed using the Functional Connectivity Toolbox (CONN). Our results demonstrate that connectivity of hippocampus to the precuneus cortex and brain stem was significantly stronger in males than in females. These results improve our current understanding of the role of hippocampus-precuneus cortex and hippocampus-brainstem connectivity in sex differences in MCI. Understanding the contribution of impaired functional connectivity sex differences may aid in the development of sex specific precision medicine to manipulate hippocampal-precuneus cortex and hippocampal-brainstem connectivity to decrease the progression of MCI to AD.

Multi-Phase Locking Value: A Generalized Method for Determining Instantaneous Multi-Frequency Phase Coupling.

BACKGROUND: Many physical, biological and neural systems behave as coupled oscillators, with characteristic phase coupling across different frequencies. Methods such as n : m phase locking value (where two coupling frequencies are linked as: mf 1 = nf 2) and bi-phase locking value have previously been proposed to quantify phase coupling between two resonant frequencies (e.g. f, 2f/3) and across three frequencies (e.g. f 1, f 2, f 1 + f 2), respectively. However, the existing phase coupling metrics have their limitations and limited applications. They cannot be used to detect or quantify phase coupling across multiple frequencies (e.g. f 1, f 2, f 3, f 4, f 1 + f 2 + f 3 - f 4), or coupling that involves non-integer multiples of the frequencies (e.g. f 1, f 2, 2f 1/3 + f 2/3). NEW METHODS: To address the gap, this paper proposes a generalized approach, named multi-phase locking value (M-PLV), for the quantification of various types of instantaneous multi-frequency phase coupling. Different from most instantaneous phase coupling metrics that measure the simultaneous phase coupling, the proposed M-PLV method also allows the detection of delayed phase coupling and the associated time lag between coupled oscillators. RESULTS: The M-PLV has been tested on cases where synthetic coupled signals are generated using white Gaussian signals, and a system comprised of multiple coupled Rössler oscillators, as well as a human subject dataset. Results indicate that the M-PLV can provide a reliable estimation of the time window and frequency combination where the phase coupling is significant, as well as a precise determination of time lag in the case of delayed coupling. This method has the potential to become a powerful new tool for exploring phase coupling in complex nonlinear dynamic systems.

Urinary Biomarkers of Oxidative Stress in Aging: Implications for Prediction of Accelerated Biological Age in Prospective Cohort Studies.

Background: Aging is a major risk factor for a range of chronic diseases. Oxidative stress theory of aging has been previously proposed as one of the mechanisms responsible for the age-related decline in organ/tissue function and the development of age-related diseases. Urine contains rich biological information on the health status of every major organ system and can be an important noninvasive source for biomarkers of systemic oxidative stress in aging. Aims: The objective of this cross-sectional study was to validate a novel panel of urinary oxidative stress biomarkers. Methods: Nucleic acid oxidation adducts and oxidative damage markers of lipids and proteins were assessed in urine samples from nondiabetic and currently nonsmoking subjects (n = 198) across different ages (20 to 89 years old). Urinary parameters and chronological age were correlated then the biological age of enrolled individuals was determined from the urinary oxidative stress markers using the algorithm of Klemera and Doubal. Results: Our findings showed that 8-oxo-7,8-deoxyguanosine (8-oxoG), 8-oxo-7,8-dihydroguanosine (8-OHdG), and dityrosine (DTyr) positively correlated with chronological age, while the level of an F2-isoprostane (iPF2 α-VI) correlated negatively with age. We found that 8-oxoG, DTyr, and iPF2 α-VI were significantly higher among accelerated agers compared to nonaccelerated agers and that a decision tree model could successfully identify accelerated agers with an accuracy of >92%. Discussion. Our results indicate that 8-oxoG and iPF2 α-VI levels in the urine reveal biological aging. Conclusion: Assessing urinary biomarkers of oxidative stress may be an important approach for the evaluation of biological age by identifying individuals at accelerated risk for the development of age-related diseases.

Cortical Reorganization of Early Somatosensory Processing in Hemiparetic Stroke.

The cortical motor system can be reorganized following a stroke, with increased recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to movement impairments. This proof-of-concept study assessed somatosensory evoked potentials (SEPs), P50 and N100, in hemiparetic stroke participants and age-matched controls using high-density electroencephalograph (EEG) recordings during tactile finger stimulation. The laterality index was calculated to determine the hemispheric dominance of the SEP and re-confirmed with source localization. The study found that latencies of P50 and N100 were significantly delayed in stroke brains when stimulating the paretic hand. The amplitude of P50 in the contralateral (to stimulated hand) hemisphere was negatively correlated with the Fügl-Meyer upper extremity motor score in stroke. Bilateral cortical responses were detected in stroke, while only contralateral cortical responses were shown in controls, resulting in a significant difference in the laterality index. These results suggested that somatosensory reorganization after stroke involves increased recruitment of ipsilateral cortical regions, especially for the N100 SEP component. This reorganization delays the latency of somatosensory processing after a stroke. This research provided new insights related to the somatosensory reorganization after stroke, which could enrich future hypothesis-driven therapeutic rehabilitation strategies from a sensory or sensory-motor perspective.

Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma.

We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from Solanum nigrum Linn, against HCC. Recently, the U.S. FDA approved Utt-B as an 'orphan drug' against HCC. The current study validates the superior anti-HCC efficacy of Utt-B over sorafenib, the first-line treatment option against HCC. The therapeutic efficacies of Utt-B vs. sorafenib against HCC were compared in vitro, using various liver cancer cell lines and in vivo, utilizing NOD.CB17-Prkdcscid/J mice bearing human HCC xenografts. Our data indicate that Utt-B holds an augmented anti-HCC efficacy over sorafenib. Our previous report demonstrated the pharmacological safety of Utt-B in Chang Liver, the normal immortalized hepatocytes, and in the acute and chronic toxicity murine models even at elevated Utt-B concentrations. Here, we show that higher concentrations of sorafenib induce severe toxicity, in Chang Liver, as well as in acute and chronic in vivo models, indicating that, apart from the superior therapeutic benefit over sorafenib, Utt-B is a pharmacologically safer molecule, and the drug-induced undesirable effects can, thus, be substantially alleviated in the context of HCC chemotherapy. Clinical studies in HCC patients utilizing Utt-B, is a contiguous key step to promote this drug to the clinic.

Machine learning paradigm for dynamic contrast-enhanced MRI evaluation of expanding bladder.

Delineation of the bladder under a dynamic contrast enhanced (DCE)-MRI protocol requires robust segmentation. However, this method is subject to errors due to variations in the content of fluid within the bladder, as well as presence of air and similarity of signal intensity in adjacent organs. Introduction of the contrast media into the bladder also causes signal errors due to alterations in the shape of the bladder. To circumvent such errors, and to improve the accuracy, we adapted a machine learning paradigm that utilizes the global bladder shape. The ML system first uses the combination of low level image processing tools such as filtering, and mathematical morphology as preprocessing step. We use neural network for training the network using extracted features and application of trained model on test slices to compute the delineated bladder shapes. This ML-based integrated system has an accuracy of 90.73% and time reduction of 65.2% in over manual delineation and can be used in clinical settings for IC/BPS patient care. Finally, we apply Jaccard Similarity Measure which we report to have a mean score of 0.933 (95% Confidence Interval 0.923, 0.944).

Low-cost preventive screening using carotid ultrasound in patients with diabetes.

Diabetes and atherosclerosis are the predominant causes of stroke and cardiovascular disease (CVD) both in low- and high-income countries. This is due to the lack of appropriate medical care or high medical costs. Low-cost 10-year preventive screening can be used for deciding an effective therapy to reduce the effects of atherosclerosis in diabetes patients. American College of Cardiology (ACC)/American Heart Association (AHA) recommended the use of 10-year risk calculators, before advising therapy. Conventional risk calculators are suboptimal in certain groups of patients because their stratification depends on (a) current blood biomarkers and (b) clinical phenotypes, such as age, hypertension, ethnicity, and sex. The focus of this review is on risk assessment using innovative composite risk scores that use conventional blood biomarkers combined with vascular image-based phenotypes. AtheroEdge™ tool is beneficial for low-moderate to high-moderate and low-risk to high-risk patients for the current and 10-year risk assessment that outperforms conventional risk calculators. The preventive screening tool that combines the image-based phenotypes with conventional risk factors can improve the 10-year cardiovascular/stroke risk assessment.

The crossed frontal aslant tract: A possible pathway involved in the recovery of supplementary motor area syndrome.

Introduction: Supplementary motor area (SMA) syndrome is a constellation of temporary symptoms that may occur following tumors of the frontal lobe. Affected patients develop akinesia and mutism but often recover within weeks to months. With our own case examples and with correlations to fiber tracking validated by gross anatomical dissection as ground truth, we describe a white matter pathway through which recovery may occur. Methods: Diffusion spectrum imaging from the Human Connectome Project was used for tractography analysis. SMA outflow tracts were mapped in both hemispheres using a predefined seeding region. Postmortem dissections of 10 cadaveric brains were performed using a modified Klingler technique to verify the tractography results. Results: Two cases were identified in our clinical records in which patients sustained permanent SMA syndrome after complete disconnection of the SMA and corpus callosum (CC). After investigating the postoperative anatomy of these resections, we identified a pattern of nonhomologous connections through the CC connecting the premotor area to the contralateral premotor and SMAs. The transcallosal fibers have projections from the previously described frontal aslant tract (FAT) and thus, we have termed this path the "crossed FAT." Conclusions: We hypothesize that this newly described tract may facilitate recovery from SMA syndrome by maintaining interhemispheric connectivity through the supplementary motor and premotor areas.

Radiological Estimation of Intracranial Blood Volume and Occurrence of Hydrocephalus Determines Stress-Induced Hyperglycemia After Aneurysmal Subarachnoid Hemorrhage.

Acute phase after aneurysmal subarachnoid hemorrhage (aSAH) is associated with several metabolic derangements including stress-induced hyperglycemia (SIH). The present study is designed to identify objective radiological determinants for SIH to better understand its contributory role in clinical outcomes after aSAH. A computer-aided detection tool was used to segment admission computed tomography (CT) images of aSAH patients to estimate intracranial blood and cerebrospinal fluid volumes. Modified Graeb score (mGS) was used as a semi-quantitative measure to estimate degree of hydrocephalus. The relationship between glycemic gap (GG) determined SIH, mGS, and estimated intracranial blood and cerebrospinal fluid volumes were evaluated using linear regression. Ninety-four [94/187 (50.3%)] among the study cohort had SIH (defined as GG > 26.7 mg/dl). Patients with SIH had 14.3 ml/1000 ml more intracranial blood volume as compared to those without SIH [39.6 ml (95% confidence interval, CI, 33.6 to 45.5) vs. 25.3 ml (95% CI 20.6 to 29.9), p = 0.0002]. Linear regression analysis of mGS with GG showed each unit increase in mGS resulted in 1.2 mg/dl increase in GG [p = 0.002]. Patients with SIH had higher mGS [median 4.0, interquartile range, IQR 2.0-7.0] as compared to those without SIH [median 2.0, IQR 0.0-6.0], p = 0.002. Patients with third ventricular blood on admission CT scan were more likely to develop SIH [67/118 (56.8%) vs. 27/69 (39.1%), p = 0.023]. Hence, the present study, using unbiased SIH definition and objective CT scan parameters, reports "dose-dependent" radiological features resulting in SIH. Such findings allude to a brain injury-stress response-neuroendocrine axis in etiopathogenesis of SIH.

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.

The accuracy of magnetic resonance imaging in the assessment of glenohumeral articular degenerative disease.

Degenerative joint disease is a major source of disability in the world with over 43 million individuals suffering from the affliction in the United States alone. It is the most common cause of activity limitation in individuals over 65 years of age. While much of the focus in recent years has been on osteoarthritis of the hips and knees, shoulder degenerative disease is becoming a more commonly recognized source of morbidity with a wide range of associated lifestyle-limiting disabilities. At the same time therapeutic options for treatment of degenerative joint disease are rapidly increasing, both medically and surgically. This combination of factors makes it necessary to determine a reliable, noninvasive means by which to accurately diagnose the early changes of shoulder degenerative disease. The clinical diagnosis of shoulder osteoarthritis is extremely challenging. There are numerous existing mimickers such as rotator cuff injuries, bursitis, and impingement syndrome. While the conventional radiographic findings are well recognized, they are generally late developments in the course of the disease when therapeutic options are more limited and less effective. Additionally, plain film evaluation has poor sensitivity for the detection of many of the alternative diagnoses that may underlie chronic shoulder pain. Though correlative findings are seen in MR imaging, its role in evaluating glenohumeral degenerative changes has been limited, with much of the focus being on the identification of tendinous and ligamentous disease or osseous tumors. A retrospective analysis is presented which demonstrates the efficacy of MR imaging in assessing GHJ OA, as well as shows that dedicated evaluation for specific degenerative findings results in improved detection rates of GHJ degenerative disease. It is believed that with improved detection and reporting, improved clinical care for this prevalent disorder may be achieved.

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.

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

INTRODUCTION: 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. METHODS: Data of 10 healthy adult controls from the Human Connectome Project were used for tractography analysis. All IPL connections were mapped in both hemispheres, and distances were recorded between cortical landmarks and major tracts. Ten postmortem dissections were then performed using a modified Klingler technique to serve as ground truth. RESULTS: We identified three major types of connections of the IPL. (1) Short association fibers connect the supramarginal and angular gyri, and connect both of these gyri to the superior parietal lobule. (2) Fiber bundles from the IPL connect to the frontal lobe by joining the superior longitudinal fasciculus near the termination of the Sylvian fissure. (3) Fiber bundles from the IPL connect to the temporal lobe by joining the middle longitudinal fasciculus just inferior to the margin of the superior temporal sulcus. CONCLUSIONS: We present a summary of the relevant anatomy of the IPL as part of a larger effort to understand the anatomic connections of related networks. This study highlights the principle white-matter pathways and highlights key underlying connections.

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.