Terence Z Wong

University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

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Publications (65)240.16 Total impact

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    ABSTRACT: OBJECTIVE. Hypoxia is a characteristic of many tumors and portends a worse prognosis in lung, cervical, prostate, and rectal cancers. Unlike the others, lung cancers present a unique challenge in measuring hypoxia, with invasive biopsies and higher rates of complications. Noninvasive imaging studies detecting hypoxia using isotopes of copper-diacetyl-bis(N4-methylthiosemicarbazone) ((62)Cu-ATSM) have predicted prognosis and treatment outcomes in some small feasibility trials. These images, however, may not identify all areas of hypoxia. Hence, we hypothesize that the addition of another PET imaging agent, copper-pyruvaldehyde-bis(N4-methylthiosemicarbazone) ((62)Cu-PTSM), which can detect areas of perfusion, can augment the information obtained in (62)Cu-ATSM PET scans. SUBJECTS AND METHODS. To characterize tumors on the basis of both perfusion and hypoxia, 10 patients were studied using both (62)Cu-ATSM and (62)Cu-PTSM PET scans. In addition, proteomic arrays looking at specific proangiogenic, survival, and proinflammatory targets were assessed. RESULTS. Six of 10 patients had evaluable PET scans. Our initial experience of characterizing lung tumor hypoxia using (62)Cu-ATSM and (62)Cu-PTSM PET scans showed that visualization of areas with hypoxia normalized for perfusion is feasible. All studied tumors exhibited some hypoxia. Despite the small sample size, a positive relationship was noted between epidermal growth factor levels and (62)Cu-ATSM-detected hypoxia. CONCLUSION. This initial series of (62)Cu-ATSM and (62)Cu-PTSM PET scans shows that evaluating lung masses by visualizing hypoxia and perfusion is a feasible and novel technique to provide more information. Further investigation is warranted to assess the potential role of (62)Cu-ATSM and (62)Cu-PTSM PET techniques combined with proteomics as alternatives to invasive biopsy techniques in clinical care.
    American Journal of Roentgenology 11/2013; 201(5):W698-706. · 2.90 Impact Factor
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    ABSTRACT: To determine interreader agreement and diagnostic accuracy across varying levels of reader experience using qualitative and quantitative methods of evaluating adrenal nodules using ((18)F)-fluorodeoxyglucose-positron emission tomography/computed tomography. 132 adrenal nodules (96 adenomas, 36 metastases) were retrospectively identified in 105 patients (49 men and 56 women, mean age 66 years, age range 45-85 years) with a history of lung cancer who underwent ((18)F)-fluorodeoxyglucose-positron emission tomography/computed tomography. For each nodule, three readers independently performed one qualitative and two quantitative measurements: visual assessment, standardized uptake value (SUVmax), and standard uptake ratio (SUVratio). Interreader agreement was calculated using percent agreement with κ statistic for qualitative analysis and intraclass correlation coefficient (ICC) for quantitative analysis. Accuracy, sensitivity, and specificity for distinguishing benign from malignant adrenal nodules were calculated for each method. Percent agreement between readers for visual (qualitative) assessment was 92% to 96% and κ statistic was 0.79 to 0.90 (95% confidence limits 0.66-0.99). ICC for SUVmax was 92% to 99% (95% CL 0.8-1.0), and ICC for SUVratio was 89% to 99% (95% CL 0.74-0.99). For diagnosis of malignancy, mean sensitivity and specificity for visual assessment were 80% and 97%, respectively. Mean sensitivity and specificity for SUVmax were 91% and 81%, respectively; for SUVratio, 90% and 80%. Mean diagnostic accuracy was 93%, 83%, and 84% for visual assessment, SUVmax, and SUVratio, respectively. Excellent interreader agreement is seen for quantitative and qualitative methods of distinguishing benign from malignant adrenal nodules. Qualitative analysis demonstrated higher accuracy but lower sensitivity compared with quantitative analysis.
    Academic radiology 08/2013; 20(8):923-9. · 2.09 Impact Factor
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    ABSTRACT: (18)F-florbetapir positron emission tomography (PET) imaging of the brain is now approved by the Food and Drug Administration (FDA) approved for estimation of β-amyloid neuritic plaque density when evaluating patients with cognitive impairment. However, its impact on clinical decision-making is not known. We present 11 cases (age range 67-84) of cognitively impaired subjects in whom clinician surveys were done before and after PET scanning to document the theoretical impact of amyloid imaging on the diagnosis and treatment plan of cognitively impaired subjects. Subjects have been clinically followed for about 5 months after the PET scan. Negative scans occurred in five cases, leading to a change in diagnosis for four patients and a change in treatment plan for two of these cases. Positive scans occurred in six cases, leading to a change in diagnosis for four patients and a change in treatment plan for three of these cases. Following the scan, only one case had indeterminate diagnosis. Our series suggests that both positive and negative florbetapir PET scans may enhance diagnostic certainty and impact clinical decision-making. Controlled longitudinal studies are needed to confirm our data and determine best practices.
    Neurocase 05/2013; · 1.05 Impact Factor
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    ABSTRACT: The purpose of this study was to determine whether certain factors in the preparation and use of (99m)Tc-sulfur colloid affected the number of sentinel lymph nodes (SLNs) detected during SLN mapping and during intraoperative SLN identification. The factors that were investigated included the use of a dry heat block versus a hot water bath to heat the (99m)Tc-sulfur colloid bulk vial, amount of (99m)Tc04(-) added to form the sulfur colloid particles, time between the unit dose calibration and the injection of the dose, and breast quadrant in which the injection occurred. METHODS: Data were collected retrospectively and quantitatively analyzed from images and reports of 488 patients with breast cancer who had undergone SLN mapping and intraoperative SLN identification from January 1, 2008, to June 30, 2011, inclusive. The dependent variables assessed were the number of SLNs visualized during lymphoscintigraphy, number of radioactive SLNs removed during surgery, and total number of lymph nodes removed intraoperatively. RESULTS: There was no significant difference in outcomes when comparing the amount of (99m)Tc04(-) added during the preparation process to form the sulfur colloid particles, time between the unit dose calibration time and the time that the unit doses were injected, or location in the breast tissue in which the unit dose was administered. Initially, there were observed significant differences in outcomes when the heating methods used to prepare the (99m)Tc-sulfur colloid were compared. When the increased number of patients who were administered a calibrated unit dose activity of 74 MBq in the group using a dry heat block preparation method was taken into account, however, the findings were not significant. CONCLUSION: The use of a dry heat block versus a hot water bath to heat the (99m)Tc-sulfur colloid bulk vial, amount of (99m)Tc04(-) added to form sulfur colloid particles, time between the unit dose calibration and the injection of the dose, and breast quadrant in which the injection occurred do not affect the number of SLNs detected during SLN mapping and during intraoperative SLN identification.
    Journal of Nuclear Medicine Technology 04/2013;
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    ABSTRACT: Background Although it is well known that many clinical and genetic factors have been associated with beta-amyloid deposition, few studies have examined the interactions of such factors across different stages of Alzheimer's pathogenesis.Methods We used 18F-florbetapir F18 PET imaging to quantify neuritic beta-amyloid plaque density across four cortical regions in 602 elderly (55–94 years) subjects from the national ADNI biomarker study. The group comprised of 194 normal elderly, 212 early mild cognitive impairment [EMCI], 132 late mild cognitive impairment [LMCI], and 64 mild Alzheimer's (AD).FindingsIn a model incorporating multiple predictive factors, the effect of apolipoprotein E ε4 and diagnosis was significant on all four cortical regions. The highest signals were seen in cingulate followed by frontal and parietal with lowest signals in temporal lobe (p < 0.0001). The effect of apolipoprotein E ε4 (Cohen's D 0.96) on beta-amyloid plaque density was approximately twice as large as the effect of a diagnosis of AD (Cohen's D 0.51) and thrice as large as the effect of a diagnosis of LMCI (Cohen's D 0.34) (p < 0.0001). Surprisingly, ApoE ε4 + normal controls had greater mean plaque density across all cortical regions than ε4 − EMCI and ε4 − LMCI (p < 0.0001, p = 0.0009) and showed higher, though non-significant, mean value than ε4 − AD patients (p < 0.27). ApoE ε4 + EMCI and LMCI subjects had significantly greater mean plaque density across all cortical regions than ε4 − AD patients (p < 0.027, p < 0.0001).InterpretationNeuritic amyloid plaque load across progressive clinical stages of AD varies strongly by ApoE4 genotype. These findings support the need for better pathology-based and supported diagnosis in routine practice. Our data also provides additional evidence for a temporal offset between amyloid deposition and clinically relevant symptoms.
    NeuroImage 04/2013; 78:474–480. · 6.25 Impact Factor
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    ABSTRACT: Radium-223 chloride ((223)Ra; Alpharadin) is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153), (223)Ra delivers a high quantity of energy per track length with short tissue penetration. This review describes the mechanism, radiobiology, and preclinical development of (223)Ra and discusses the clinical data currently available regarding its safety and efficacy profile. Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database. Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab), which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153), which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC). Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, (223)Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, (223)Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel agents.
    Cancer Management and Research 01/2013; 5:1-14.
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    ABSTRACT: Neurological and neurocognitive dysfunction occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery every year. Perioperative cognitive deficits have been shown to persist after discharge and up to several years after surgery. More importantly, perioperative cognitive decline is predictive of long-term cognitive dysfunction, reduced quality of life and increased mortality. The proposed mechanisms to explain the cognitive decline associated with cardiac surgery include the neurotoxic accumulation of β-amyloid. This study will be the first to provide molecular imaging to assess the relationship between neocortical β-amyloid deposition and postoperative cognitive dysfunction. 40 patients providing informed consent for participation in this Institutional Review Board-approved study and undergoing cardiac (coronary artery bypass graft (CABG), valve or CABG+valve) surgery with cardiopulmonary bypass will be enrolled based on defined inclusion and exclusion criteria. At 6 weeks after surgery, participants will undergo (18)F-florbetapir positron emission tomography imaging to assess neocortical β-amyloid burden along with a standard neurocognitive battery and blood testing for apolipoprotein E ε-4 genotype. The results will be compared to those of 40 elderly controls and 40 elderly patients with mild cognitive impairment who have previously completed (18)F-florbetapir imaging. This study has been approved by the Duke University Institutional Review Board. The results will provide novel mechanistic insights into postoperative cognitive dysfunction that will inform future studies into potential treatments or preventative therapies of long-term cognitive decline after cardiac surgery.
    BMJ Open 01/2013; 3(9):e003669. · 2.06 Impact Factor
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    ABSTRACT: Purpose: Abnormalities in single photon emission computed tomography (SPECT) perfusion within the lung and heart are often detected following radiation for tumors in∕around the thorax (e.g., lung cancer or left-sided breast cancer). The presence of SPECT perfusion defects is determined by comparing pre- and post-RT SPECT images. However, RT may increase the density of the soft tissue surrounding the lung∕heart (e.g., chest wall∕breast) that could possibly lead to an "apparent" SPECT perfusion defect due to increased attenuation of emitted photons. Further, increases in tissue effective depth will also increase SPECT photon attenuation and may lead to "apparent" SPECT perfusion defects. The authors herein quantitatively assess the degree of density changes and effective depth in soft tissues following radiation in a series of patients on a prospective clinical study.Methods: Patients receiving thoracic RT were enrolled on a prospective clinical study including pre- and post-RT thoracic computed tomography (CT) scans. Using image registration, changes in tissue density and effective depth within the soft tissues were quantified (as absolute change in average CT Hounsfield units, HU, or tissue thickness, cm). Changes in HU and tissue effective depth were considered as a continuous variable. The potential impact of these tissue changes on SPECT images was estimated using simulation data from a female SPECT thorax phantom with varying tissue densities.Results: Pre- and serial post-RT CT images were quantitatively studied in 23 patients (4 breast cancer, 19 lung cancer). Data were generated from soft tissue regions receiving doses of 20-50 Gy. The average increase in density of the chest was 5 HU (range 46 to -69). The average change in breast density was a decrease of -1 HU (range 13 to -13). There was no apparent dose response in neither the dichotomous nor the continuous analysis. Seventy seven soft tissue contours were created for 19 lung cancer patients. The average change in tissue effective depth was +0.2 cm (range -1.9 to 2.2 cm). The changes in HU represent a <2% average change in tissue density. Based on simulation, the small degree of density and tissue effective depth change is unlikely to yield meaningful changes in either SPECT lung or heart perfusion.Conclusions: RT doses of 20-50 Gy can cause up to a 46 HU increase in soft tissue density 6 months post-RT. Post-RT soft tissue effective depth may increase by 2.0 cm. These modest increases in soft tissue density and effective depth are unlikely to be responsible for the perfusion changes seen on post-RT SPECT lung or heart scans. Further, there was no clear dose response of thesoft tissue density changes. Ultimately, the authors findings suggest that prior perfusion reports do reflect changes in the physiology of the lungs and heart.
    Medical Physics 12/2012; 39(12):7644-9. · 2.91 Impact Factor
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    ABSTRACT: The use of Tc-99m-Sestamibi in molecular breast imaging is common due to its preferential uptake in malignant tissue. However, quantification of the baseline uptake in normal, healthy breast tissue is not possible using planar-imaging devices. Using our dedicated breast SPECT-CT system, an IRB approved pilot study is underway to quantify mean activity in normal breast tissue, and to differentiate uptake between adipose and glandular tissues. A cohort of patients at normal breast cancer risk undergoing another diagnostic Sestamibi study was imaged using the breast SPECT-CT system. SPECT images were corrected and quantitatively reconstructed using previously developed methods, and registered with the CT images. The CT images were segmented, and the average activity concentration was measured for glandular, adipose, and total breast tissue. Results indicate no preferential uptake between tissues and low average uptake, which may be used to determine a universal threshold for cancer detection.
    Proceedings of the 11th international conference on Breast Imaging; 07/2012
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    ABSTRACT: Accurate clinical diagnosis of Alzheimer's disease (AD) is vital but has remained chal-lenging because of the dichotomy between clinical diagnosis (made using cognitive tests) and definitive diagnosis (which requires pathological evidence of -amyloid plaques and tangles in the brain) [1–4] . A recent clinical-autopsy correlative study of more than 900 cases seen at the very best US memory centers found that nearly 40% of patients clinically diagnosed with non-AD dementia had postmortem histopathology consistent with AD [2] . Likewise, studies suggest that up to 30% of patients clinically diagnosed with possible or probable AD may not meet postmortem pathologic criteria for AD [1–4] . It is important to accurately differentiate the early stage of AD from other types of cognitive disorders, which may have different prog-nosis and different potential for treatment [1–4] . Efforts to bridge the gap between clinical and pathological diagnosis have led to the development of PET tracers with high affinity for -amyloid neuritic plaques, such as 11 C-PiB, 18 F-florbetaben and 18 F-florbetapir [1] as well as the recent US marketing of florbetapir for clinical use [1, 3–7] . Although these amyloid PET tracers correlate well with postmortem histopathology [1, 3] , less is known about their impact on clinical decision-making and patient outcomes. The need to assess the effectiveness of amyloid imaging in clinical practice is addressed in this issue of Dementia and Geriatric Cognitive Disorders Extra by Frederiksen et al. [3] . The study examined the diagnostic value of PiB-PET imaging in 57 memory clinic patients (mean age: 65.7 years) who had cognitive impairment of uncertain etiology despite extensive clinical workup prior to the scan. The PiB-PET scan led to diagnostic reclassification in a total of 13 (23%) patients, most commonly in cases with indeterminate etiology prior to the scan. The number of patients that had to undergo the scan for one change in diagnosis (num-ber needed to test, NNT) was 4.4 for all diagnostic categories. Furthermore, the clinicians' overall confidence increased in 28 (49%) patients and their confidence to confirm or rule out AD increased in the majority of cases, including cases that were not reclassified. As such, this
    Dementia and geriatric cognitive disorders extra. 01/2012; 2(1):649-51.
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    ABSTRACT: A pilot study is underway to quantify in vivo the uptake and distribution of Tc-99m Sestamibi in subjects without previous history of breast cancer using a dedicated SPECT-CT breast imaging system. Subjects undergoing diagnostic parathyroid imaging studies were consented and imaged as part of this IRB-approved breast imaging study. For each of the seven subjects, one randomly selected breast was imaged prone-pendant using the dedicated, compact breast SPECT-CT system underneath the shielded patient support. Iteratively reconstructed and attenuation and/or scatter corrected images were coregistered; CT images were segmented into glandular and fatty tissue by three different methods; the average concentration of Sestamibi was determined from the SPECT data using the CT-based segmentation and previously established quantification techniques. Very minor differences between the segmentation methods were observed, and the results indicate an average image-based in vivo Sestamibi concentration of 0.10 ± 0.16 μCi/mL with no preferential uptake by glandular or fatty tissues.
    Journal of Oncology 01/2012; 2012:146943.
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    Aditya Bansal, Terence Z. Wong, Timothy R. DeGrado
    Advances in the Biology, Imaging and Therapies for Glioblastoma, 11/2011; , ISBN: 978-953-307-284-5
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    ABSTRACT: Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monitoring the delivery of therapeutic agents that would permit technical optimization and enhanced therapeutic efficacy. To determine whether a readily available small-molecule MRI contrast agent, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), could effectively track the distribution of larger therapeutic agents. Gd-DTPA was coinfused with the larger molecular tracer, I-labeled human serum albumin (I-HSA), during CED of an EGFRvIII-specific immunotoxin as part of treatment for a patient with glioblastoma. Infusion of both tracers was safe in this patient. Analysis of both Gd-DTPA and I-HSA during and after infusion revealed a high degree of anatomical and volumetric overlap. Gd-DTPA may be able to accurately demonstrate the anatomic and volumetric distribution of large molecules used for antitumor therapy with high resolution and in combination with fluid-attenuated inversion recovery (FLAIR) imaging, and provide additional information about leaks into cerebrospinal fluid spaces and resection cavities. Similar studies should be performed in additional patients to validate our findings and help refine the methodologies we used.
    Neurosurgery 03/2011; 69(3):668-76. · 2.53 Impact Factor
  • David S Yoo, Terence Z Wong, David M Brizel
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    ABSTRACT: The field of radiation oncology relies heavily on imaging modalities. From initial consultation to treatment completion, images are used to guide nearly every step of the patient encounter. Technological advances in diagnostic radiology continue to be readily incorporated into clinical practice, with adaptive and functional studies able to extract and display ever more physical and novel biological data about patients and their tumors. At the same time, no imaging technique can address all the uncertainties inherent in cancer therapy. The application, interpretation, and limitations of various imaging modalities are discussed from a radiation oncology perspective.
    Seminars in Ultrasound CT and MRI 12/2010; 31(6):444-61. · 1.29 Impact Factor
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    ABSTRACT: OBJECTIVE: There is growing interest in using PET/CT for evaluating early response to therapy in cancer treatment. Although widely available and convenient to use, standardized uptake value (SUV) measurements can be influenced by a variety of biologic and technologic factors. Many of these factors can be addressed with close attention to detail and appropriate quality control. This article will review factors potentially affecting SUV measurements and provide recommendations on ways to minimize when using serial PET to assess early response to therapy. CONCLUSION: Scanner and reconstruction parameters can significantly affect SUV measurements. When using serial SUV measurements to assess early response to therapy, imaging should be performed on the same scanner using the same image acquisition and reconstruction protocols. In addition, attention to detail is required for accurate determination of the administered radiopharmaceutical dose.
    American Journal of Roentgenology 08/2010; 195(2):310-20. · 2.90 Impact Factor
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    ABSTRACT: Isolated colonic schwannomas are rare gastrointestinal mesenchymal tumors; only a small number of cases have been reported. The incidence is 2% to 6% of all submucosal tumors of the gastrointestinal tract. They are thought to be distinctive from conventional schwannomas that arise in soft tissue or the central nervous system. Although colonic schwannomas are considered benign, these lesions may demonstrate intense FDG avidity, which makes them indistinguishable from the more common potentially malignant gastrointestinal stromal tumor.
    Clinical nuclear medicine 03/2010; 35(3):181-3. · 3.92 Impact Factor
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    ABSTRACT: To establish accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas. 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. 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. 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.
    Medical Physics 11/2009; 36(11):4848-58. · 2.91 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the diagnostic value of a hybrid (111)In-capromab pendetide fused computed tomography (CT) scan in detecting seminal vesicle invasion (SVI) in the setting of recurrent prostate cancer following primary in situ therapy. The study population comprised 59 patients, who biochemically failed primary in situ treatment based on American Society for Therapeutic Radiology and Oncology criteria. The patients underwent an (111)In-capromab pendetide/CT scan at the time of biochemical failure with a prostate (12-core) and seminal vesicle (SV) (8-core) biopsy. The diagnostic properties of the scan and magnetic resonance imaging (MRI) in detecting SVI compared to an SV biopsy were calculated. In total, eight (14%) patients had a positive SV biopsy after primary in situ prostate cancer treatment. Nine (15%) patients had positive uptake of the scan in the SV. When comparing the SV scan results to the SV biopsy, the sensitivity, specificity, positive predictive value, and negative predictive value were 37.5%, 88.2%, 33.3%, and 90.0% (95% confidence interval: 0.44-0.81), respectively. In contrast, the ability of MRI to detect SVI was 50.0%, 81.3%, 40.0%, and 86.7% (95% confidence interval: 0.46-0.85), respectively. Although the sensitivity and positive predictive value of the (111)In-capromab pendetide/CT scan are low, its specificity and negative predictive value are high. Based on these findings, the ability of the (111)In-capromab pendetide/CT scan to detect SVI seems to be comparable with MRI.
    International Journal of Urology 10/2009; 16(12):971-5. · 1.73 Impact Factor
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    ABSTRACT: To assess the time and regional dependence of radiation therapy (RT)-induced reductions in regional lung perfusion 0.1-12 years post-RT, as measured by single photon emission computed tomography (SPECT) lung perfusion. Between 1991 and 2005, 123 evaluable patients receiving RT for tumors in/around the thorax underwent SPECT lung perfusion scans before and serially post-RT (0.1-12 years). Registration of pre- and post-RT SPECT images with the treatment planning computed tomography, and hence the three-dimensional RT dose distribution, allowed changes in regional SPECT-defined perfusion to be related to regional RT dose. Post-RT follow-up scans were evaluated at multiple time points to determine the time course of RT-induced regional perfusion changes. Population dose response curves (DRC) for all patients at different time points, different regions, and subvolumes (e.g., whole lungs, cranial/caudal, ipsilateral/contralateral) were generated by combining data from multiple patients at similar follow-up times. Each DRC was fit to a linear model, and differences statistically analyzed. In the overall groups, dose-dependent reductions in perfusion were seen at each time post-RT. The slope of the DRC increased over time up to 18 months post-RT, and plateaued thereafter. Regional differences in DRCs were only observed between the ipsilateral and contralateral lungs, and appeared due to tumor-associated changes in regional perfusion. Thoracic RT causes dose-dependent reductions in regional lung perfusion that progress up to approximately 18 months post-RT and persists thereafter. Tumor shrinkage appears to confound the observed dose-response relations. There appears to be similar dose response for healthy parts of the lungs at different locations.
    International journal of radiation oncology, biology, physics 08/2009; 76(2):425-32. · 4.59 Impact Factor
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    ABSTRACT: 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. To use a novel morpho-physiological tumour score (MPTS) generated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict response to treatment. 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. 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. 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.
    International Journal of Hyperthermia 08/2009; 25(6):405-15. · 2.59 Impact Factor

Publication Stats

1k Citations
240.16 Total Impact Points

Institutions

  • 2012
    • University of North Carolina at Chapel Hill
      • Department of Radiation Oncology
      Chapel Hill, NC, United States
  • 2001–2011
    • Duke University Medical Center
      • • Division of Neurosurgery
      • • Department of Radiation Oncology
      • • Department of Radiology
      Durham, NC, United States
  • 2005–2010
    • Duke University
      • Department of Biomedical Engineering (BME)
      Durham, NC, United States
  • 2007
    • Boston College, USA
      Boston, Massachusetts, United States