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1.
Emerg Radiol ; 31(2): 167-178, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38302827

ABSTRACT

PURPOSE: The AAST Organ Injury Scale is widely adopted for splenic injury severity but suffers from only moderate inter-rater agreement. This work assesses SpleenPro, a prototype interactive explainable artificial intelligence/machine learning (AI/ML) diagnostic aid to support AAST grading, for effects on radiologist dwell time, agreement, clinical utility, and user acceptance. METHODS: Two trauma radiology ad hoc expert panelists independently performed timed AAST grading on 76 admission CT studies with blunt splenic injury, first without AI/ML assistance, and after a 2-month washout period and randomization, with AI/ML assistance. To evaluate user acceptance, three versions of the SpleenPro user interface with increasing explainability were presented to four independent expert panelists with four example cases each. A structured interview consisting of Likert scales and free responses was conducted, with specific questions regarding dimensions of diagnostic utility (DU); mental support (MS); effort, workload, and frustration (EWF); trust and reliability (TR); and likelihood of future use (LFU). RESULTS: SpleenPro significantly decreased interpretation times for both raters. Weighted Cohen's kappa increased from 0.53 to 0.70 with AI/ML assistance. During user acceptance interviews, increasing explainability was associated with improvement in Likert scores for MS, EWF, TR, and LFU. Expert panelists indicated the need for a combined early notification and grading functionality, PACS integration, and report autopopulation to improve DU. CONCLUSIONS: SpleenPro was useful for improving objectivity of AAST grading and increasing mental support. Formative user research identified generalizable concepts including the need for a combined detection and grading pipeline and integration with the clinical workflow.


Subject(s)
Tomography, X-Ray Computed , Wounds, Nonpenetrating , Humans , Tomography, X-Ray Computed/methods , Artificial Intelligence , Reproducibility of Results , Machine Learning
2.
Emerg Radiol ; 30(3): 251-265, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36917287

ABSTRACT

BACKGROUND: AI/ML CAD tools can potentially improve outcomes in the high-stakes, high-volume model of trauma radiology. No prior scoping review has been undertaken to comprehensively assess tools in this subspecialty. PURPOSE: To map the evolution and current state of trauma radiology CAD tools along key dimensions of technology readiness. METHODS: Following a search of databases, abstract screening, and full-text document review, CAD tool maturity was charted using elements of data curation, performance validation, outcomes research, explainability, user acceptance, and funding patterns. Descriptive statistics were used to illustrate key trends. RESULTS: A total of 4052 records were screened, and 233 full-text articles were selected for content analysis. Twenty-one papers described FDA-approved commercial tools, and 212 reported algorithm prototypes. Works ranged from foundational research to multi-reader multi-case trials with heterogeneous external data. Scalable convolutional neural network-based implementations increased steeply after 2016 and were used in all commercial products; however, options for explainability were narrow. Of FDA-approved tools, 9/10 performed detection tasks. Dataset sizes ranged from < 100 to > 500,000 patients, and commercialization coincided with public dataset availability. Cross-sectional torso datasets were uniformly small. Data curation methods with ground truth labeling by independent readers were uncommon. No papers assessed user acceptance, and no method included human-computer interaction. The USA and China had the highest research output and frequency of research funding. CONCLUSIONS: Trauma imaging CAD tools are likely to improve patient care but are currently in an early stage of maturity, with few FDA-approved products for a limited number of uses. The scarcity of high-quality annotated data remains a major barrier.


Subject(s)
Artificial Intelligence , Radiology , Humans , Cross-Sectional Studies , Neural Networks, Computer , Algorithms
3.
Emerg Radiol ; 22(5): 577-82, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25757460

ABSTRACT

First trimester ultrasound is commonly performed to establish dates or evaluate early pregnancy complications. With improvement in ultrasound technology, visualization of fetal structures has improved. While the emergent evaluation does not typically focus on detailed fetal anatomic evaluation (since this is typically performed at 18-20 weeks), various fetal structural abnormalities can now be visualized, especially during the late first trimester and early second trimester. We present a pictorial review of potential pitfalls encountered in early obstetric ultrasound with an emphasis on fetal structural abnormalities as well as normal fetal anatomy that can be confused with developmental abnormalities.


Subject(s)
Fetus/abnormalities , Pregnancy Complications/diagnostic imaging , Ultrasonography, Prenatal , Early Diagnosis , Female , Humans , Pregnancy
4.
J Dig Dis ; 15(10): 525-37, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25060294

ABSTRACT

OBJECTIVE: This meta-analysis aimed to compare the diagnostic accuracy of diffusion-weighted magnetic resonance imaging (DW-MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) or FDG-PET/computed tomography (CT) in evaluating and predicting pathological response to preoperative neoadjuvant chemoradiotherapy (NCRT) in patients with rectal cancer. METHODS: A comprehensive literature research was conducted to identify the relevant studies for this meta-analysis. Combined sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: A total of 33 studies including 1564 patients met the inclusion criteria. The pooled sensitivity (81% [95% CI 74-86%] vs 85% [95% CI 75-91%]) and NPV (80% [95% CI 68-89%] vs 91% [95% CI 80-95%]) for FDG-PET or FDG-PET/CT were significantly lower than those for DW-MRI (P < 0.05). No differences were observed in pooled specificity and PPV between DW-MRI and FDG-PET or FDG-PET/CT. Further subgroup analyses showed that DW-MRI had higher sensitivity on adenocarcinomas alone than on those including mucinous-type adenocarcinomas (92% [95% CI 83-99%] vs 76% [95% CI 63-90%], P = 0.00). CONCLUSIONS: DW-MRI is superior to FDG-PET or FDG-PET/CT in predicting and evaluating pathological responses to preoperative NCRT in patients with rectal cancer. However, its relatively low specificity and PPV limit its application in clinic, making it currently inappropriate to monitor such patients, especially those with mucinous-type rectal adenocarcinomas.


Subject(s)
Rectal Neoplasms/diagnosis , Chemoradiotherapy, Adjuvant/methods , Diffusion Magnetic Resonance Imaging , Fluorodeoxyglucose F18 , Humans , Multimodal Imaging/methods , Neoadjuvant Therapy/methods , Positron-Emission Tomography/methods , Publication Bias , Radiopharmaceuticals , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Tomography, X-Ray Computed/methods
5.
PLoS One ; 9(5): e98303, 2014.
Article in English | MEDLINE | ID: mdl-24879409

ABSTRACT

BACKGROUND: Specific morphologic features of hepatocellular carcinoma (HCC) on imaging have identifiable pathologic correlates as well as implications for altering surgical management and defining prognosis. In this study, we compared susceptibility-weighted imaging (SWI) to conventional techniques and correlated our findings with histopathology to determine the role of SWI in assessing morphologic features of HCC without using a contrast agent. METHODS: 86 consecutive patients with suspected HCC were imaged with MRI (including T1, T2, T2*, and SWI) and subsequently CT. 59 histologically-proven HCC lesions were identified in 53 patients. Each lesion on each imaging sequence was evaluated by two radiologists, and classified with respect to lesion morphology, signal intensity relative to surrounding hepatic parenchyma, presence of a pseudocapsule, presence of venous invasion, and internal homogeneity. RESULTS: Histopathology confirmed pseudocapsules in 41/59 lesions. SWI was able to detect a pseudocapsule in 34/41 lesions; compared to conventional T1/T2 imaging (12/41) and T2* (27/41). Mosaic pattern was identified in 25/59 lesions by histopathology; SWI confirmed this in all 25 lesions, compared to T1/T2 imaging (13/25) or T2* (18/25). Hemorrhage was confirmed by histopathology in 43/59 lesions, and visible on SWI in 41/43 lesions, compared to T1/T2 (7/43) and T2* (38/43). Venous invasion was confirmed by histopathology in 31/59 patients; SWI demonstrated invasion in 28/31 patients, compared to T1/T2 (7/31) and T2* (24/31). CONCLUSIONS: SWI is better at identifying certain morphologic features such as pseudocapsule and hemorrhage than conventional MRI without using a contrast agent in HCC patients.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Magnetic Resonance Imaging/methods , Adult , Aged , Blood Vessels/pathology , Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/complications , Female , Hemorrhage/complications , Humans , Liver Neoplasms/blood supply , Liver Neoplasms/complications , Male , Middle Aged , Neoplasm Invasiveness , Prospective Studies
6.
PLoS One ; 8(7): e69701, 2013.
Article in English | MEDLINE | ID: mdl-23861979

ABSTRACT

OBJECTIVE: To investigate the feasibility of gadolinium (Gd) contrast-enhanced magnetic resonance lymphangiography (MRL) in breast cancer patients within a typical clinical setting, and to establish a Gd-MRL protocol and identify potential MRL biomarkers for differentiating metastatic from non-metastatic lymph nodes. MATERIALS AND METHODS: 32 patients with unilateral breast cancer were enrolled and divided into 4 groups of 8 patients. Groups I, II, and III received 1.0, 0.5, and 0.3 ml of intradermal contrast; group IV received two 0.5 ml doses of intradermal contrast. MRL images were acquired on a 3.0 T system and evaluated independently by two radiologists for the number and size of enhancing lymph nodes, lymph node contrast uptake kinetics, lymph vessel size, and contrast enhancement patterns within lymph nodes. RESULTS: Group III patients had a statistically significant decrease in the total number of enhancing axillary lymph nodes and lymphatic vessels compared to all other groups. While group IV patients had a statistically significant faster time to reach the maximum peak enhancement over group I and II (by 3 minutes), there was no other statistically significant difference between imaging results between groups I, II, and IV. 27 out of 128 lymphatic vessels (21%) showed dilatation, and all patients with dilated lymphatic vessels were pathologically proven to have metastases. Using the pattern of enhancement defects as the sole criterion for identifying metastatic lymph nodes during Gd-MRL interpretation, and using histopathology as the gold standard, the sensitivity and specificity were estimated to be 86% and 95%, respectively. CONCLUSION: Gd-MRL can adequately depict the lymphatic system, can define sentinel lymph nodes, and has the potential to differentiate between metastatic and non-metastatic lymph nodes in breast cancer patients.


Subject(s)
Breast Neoplasms/diagnosis , Lymphatic System/pathology , Lymphography , Magnetic Resonance Imaging , Adult , Aged , Axilla , Breast Neoplasms/pathology , Contrast Media , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Lymphatic Vessels/pathology , Middle Aged
7.
PLoS One ; 8(7): e67731, 2013.
Article in English | MEDLINE | ID: mdl-23844077

ABSTRACT

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) of the breast is a routinely used imaging method which is highly sensitive for detecting breast malignancy. Specificity, though, remains suboptimal. Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI), an alternative dynamic contrast imaging technique, evaluates perfusion-related parameters unique from DCE MRI. Previous work has shown that the combination of DSC MRI with DCE MRI can improve diagnostic specificity, though an additional administration of intravenous contrast is required. Dual-echo MRI can measure both T1W DCE MRI and T2*W DSC MRI parameters with a single contrast bolus, but has not been previously implemented in breast imaging. We have developed a dual-echo gradient-echo sequence to perform such simultaneous measurements in the breast, and use it to calculate the semi-quantitative T1W and T2*W related parameters such as peak enhancement ratio, time of maximal enhancement, regional blood flow, and regional blood volume in 20 malignant lesions and 10 benign fibroadenomas in 38 patients. Imaging parameters were compared to surgical or biopsy obtained tissue samples. Receiver operating characteristic (ROC) curves and area under the ROC curves were calculated for each parameter and combination of parameters. The time of maximal enhancement derived from DCE MRI had a 90% sensitivity and 69% specificity for predicting malignancy. When combined with DSC MRI derived regional blood flow and volume parameters, sensitivity remained unchanged at 90% but specificity increased to 80%. In conclusion, we show that dual-echo MRI with a single administration of contrast agent can simultaneously measure both T1W and T2*W related perfusion and kinetic parameters in the breast and the combination of DCE MRI and DSC MRI parameters improves the diagnostic performance of breast MRI to differentiate breast cancer from benign fibroadenomas.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Fibroadenoma/diagnosis , Magnetic Resonance Imaging/methods , Adolescent , Adult , Aged , Area Under Curve , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Contrast Media , Diagnosis, Differential , Female , Fibroadenoma/pathology , Gadolinium DTPA , Humans , Image Interpretation, Computer-Assisted , Middle Aged , ROC Curve , Regional Blood Flow , Sensitivity and Specificity
8.
BMC Dev Biol ; 12: 38, 2012 Dec 26.
Article in English | MEDLINE | ID: mdl-23268571

ABSTRACT

BACKGROUND: Magnetic resonance imaging is a noninvasive method of evaluating embryonic development. Diffusion tensor imaging (DTI), based on the directional diffusivity of water molecules, is an established method of evaluating tissue structure. Yet embryonic motion degrades the in vivo acquisition of long-duration DTI. We used a dual-cooling technique to avoid motion artifact and aimed to investigate whether DTI can be used to monitor chick embryonic skeletal muscle development in ovo, and to investigate the correlation between quantitative DTI parameters fractional anisotropy (FA) and fiber length and quantitative histologic parameters fiber area percentage (FiberArea%) and limb length. RESULTS: From 84 normally developing chick embryos, 5 were randomly chosen each day from incubation days 5 to 18 and scanned using 3.0 Tesla magnetic resonance imaging. A dual-cooling technique is used before and during imaging. Eggs were cracked for making histological specimen after imaging. 3 eggs were serially imaged from days 5 to 18. We show that skeletal muscle fibers can be tracked in hind limb in DTI beginning with incubation day 8. Our data shows a good positive correlation between quantitative DTI and histologic parameters (FA vs FiberArea%: r= 0.943, p<0.0001; Fiber_length vs Limb_length: r=0.974, p<0.0001). The result of tracked fibers in DTI during incubation corresponds to the development of chick embryonic skeletal muscle as reported in the literature. CONCLUSION: Diffusion tensor imaging can provide a noninvasive means of evaluating skeletal muscle development in ovo.


Subject(s)
Diffusion Tensor Imaging/methods , Muscle, Skeletal/embryology , Animals , Chick Embryo/embryology , Hindlimb/embryology , Muscle Development , Muscle Fibers, Skeletal/cytology
9.
PLoS One ; 7(11): e50319, 2012.
Article in English | MEDLINE | ID: mdl-23209708

ABSTRACT

OBJECTIVE: To characterize lymphatic vessel morphology in lower extremity lymphedema using MR lymphography at 3T. STUDY DESIGN: Forty females with lower extremity lymphedema secondary to gynecologic carcinoma treatment underwent MR lymphography (MRL) at 3T. Lymphatic vessel morphology in normal and affected limbs was compared. RESULTS: The median diameter of the lymphatic vessels in swollen calf and thigh were significantly larger than that in the contralateral calf and thigh, respectively (p<0.05). The median number of lymphatic vessels visualized in normal calf was less than that in the lymphedematous calf (p<0.01), while no significant difference was found between the normal thigh and swollen thigh. Lymphatic vessel number in the affected calf was significantly greater than that in affected thigh and the mean diameter of affected calf was also significantly wider than that of affected thigh (p<0.01). Mean diameter of lymphatic vessels in the affected calf was significantly different between stage I and stage III (p<0.05), but not significantly different between stages I and II, and between stages II and III (p>0.05). The median number of lymphatic vessels for affected calf showed significant difference between stage I and stage III, and between stage II and stage III (p<0.05), but no significant difference between stage I and stage II (p>0.05). There was no significant difference in mean diameter or median number of lymphatic vessels in the affected thigh found between different stages (p>0.05). CONCLUSION: There are significant differences in the number or diameter of lymphatic vessels between normal and affected limbs and there are significant differences for affected calf between early and late stages of lymphedema; therefore, MR lymphography can be helpful in diagnosis or clinical staging for lower extremity with gynecologic oncology-related lymphedema.


Subject(s)
Carcinoma/complications , Carcinoma/pathology , Genital Neoplasms, Female/complications , Genital Neoplasms, Female/pathology , Lymphedema/diagnosis , Lymphedema/pathology , Lymphography/methods , Magnetic Resonance Spectroscopy/methods , Adult , Aged , Contrast Media/pharmacology , Female , Gadolinium DTPA/pharmacology , Humans , Image Processing, Computer-Assisted , Lower Extremity/pathology , Lymphatic Vessels/pathology , Middle Aged , Reproducibility of Results
10.
PLoS One ; 7(5): e36454, 2012.
Article in English | MEDLINE | ID: mdl-22590548

ABSTRACT

BACKGROUND: Hepatic cirrhosis is a common pathway of progressive liver destruction from multiple causes. Iron uptake can occur within the hepatic parenchyma or within the various nodules that form in a cirrhotic liver, termed siderotic nodules. Siderotic nodule formation has been shown to correlate with inflammatory activity, and while the relationship between siderotic nodule formation and malignancy remains unclear, iron distribution within hepatic nodules has known implications for the detection of hepatocellular carcinoma. We aimed to evaluate the role of abdominal susceptibility-weighted imaging in the detection of siderotic nodules in cirrhotic patients. METHODOLOGY/PRINCIPAL FINDINGS: Forty-six (46) cirrhotic patients with at least one siderotic nodule detected on previous imaging underwent both computed tomography and magnetic resonance imaging (T1-, T2-, T2*-, and susceptibility-weighted imaging) at 3.0 Tesla. Imaging data was independently analyzed by two radiologists. Siderotic nodule count was determined for each modality and imaging sequence. For each magnetic resonance imaging technique, siderotic nodule conspicuity was assessed on a 3 point scale (1 = weak, 2 = moderate, 3 = strong). More nodules were detected by susceptibility weighted imaging (n = 2935) than any other technique, and significantly more than by T2* weighted imaging (n = 1696, p<0.0001). Lesion conspicuity was also highest with susceptibility-weighted imaging, with all nodules found to be moderate (n = 6) or strong (n = 40); a statistically significant difference (p<0.001). CONCLUSIONS: Susceptibility-weighted imaging had the greatest lesion conspicuity and detected the highest number of siderotic nodules suggesting it is the most sensitive imaging technique to detect siderotic nodules in cirrhotic patients.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Liver Cirrhosis/diagnostic imaging , Adult , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Female , Humans , Liver Neoplasms/diagnostic imaging , Male , Middle Aged , Radiography
11.
J Magn Reson Imaging ; 36(4): 993-1001, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22566237

ABSTRACT

PURPOSE: To evaluate the capability of a dual-cooling technique in suppressing motion artifact and to evaluate the feasibility of the noninvasive muscle fibers tracking using DTI during chick embryonic development. MATERIALS AND METHODS: Fifteen eggs were divided into three groups of 5 eggs each (one group for each imaging sequence), and eggs were imaged every 48 h from incubation day 4; embryos were imaged in ovo using three sequences of varying duration (T1, T2, and DTI). For each sequence, three preprocessing methods were used: no-cooling (NC), single-cooling (SC), and dual-cooling (DC). Two independent observers assessed images for motion artifact. The results of different preprocessing methods used for each sequence were compared by the χ(2) test. The Cohen kappa test was used to assess the interobserver variability. RESULTS: For T1 imaging, motion artifact was adequately suppressed by both SC and DC methods (χ(2) test; P > 0.05). For T2 imaging, motion artifact was also sufficiently suppressed by both SC and DC methods (χ(2) test; P > 0.05) except incubation day 19 (χ(2) test; P < 0.001). For DTI, motion artifact was less with DC than SC after 8 days (χ(2) test; P < 0.05). Hindlimb muscle fibers of chick embryo could be serially evaluated with DTI from 8 days using dual-cooling technique. CONCLUSION: The dual-cooling technique enables DTI of chick embryo in ovo with minimal motion artifact, which permits muscle fiber tracking by DTI during chick embryonic development possible, and can improve the imaging quality of conventional MRI with long duration and those sensitive to motion.


Subject(s)
Diffusion Tensor Imaging/methods , Muscle Fibers, Skeletal/cytology , Muscle, Skeletal/cytology , Muscle, Skeletal/embryology , Prenatal Diagnosis/methods , Animals , Chick Embryo , Cold Temperature , Feasibility Studies , Sensitivity and Specificity
12.
PLoS One ; 7(3): e34009, 2012.
Article in English | MEDLINE | ID: mdl-22457809

ABSTRACT

BACKGROUND: Magnetic resonance imaging is a noninvasive method of evaluating embryonic development. Magnetic resonance diffusion tensor imaging, which is based on the measuring the directional diffusivity of water molecules, is an established method of evaluating tissue structure. Prolonged imaging times have precluded the use of embryonic diffusion tensor imaging due to motion artifact. Using temperature-based motion suppression, we aimed to investigate whether diffusion tensor imaging can be used to monitor embryonic smooth muscle development in ovo, and to determine the correlation between histologically-derived muscle fiber fraction, day of incubation and diffusion tensor imaging fractional anisotropy values and length of tracked fibers. METHODOLOGY/PRINCIPAL FINDINGS: From a set of 82 normally developing fertile chicken eggs, 5 eggs were randomly chosen each day from incubation days 5 to 18 and cooled using a dual-cooling technique prior to and during magnetic resonance imaging at 3.0 Tesla. Smooth muscle fibers of the gizzard were tracked using region of interests placed over the gizzard. Following imaging, the egg was cracked and the embryo was fixated and sectioned, and a micrograph most closely corresponding to the acquired magnetic resonance image was made. Smooth muscle fiber fraction was determined using an automated computer algorithm. CONCLUSIONS/SIGNIFICANCE: We show that diffusion tensor images of smooth muscle within the embryonic gizzard can be acquired in ovo from incubation day 11 through hatching. Length of tracked fibers and day of incubation were found to have statistical significance (p<0.05) by multiple linear regression correlation with histologic specimens of sacrificed embryos from day 11 of incubation through hatching. The morphologic pattern of development in our histologic specimens corresponds to the development of embryonic gizzard as reported in the literature. These results suggest that diffusion tensor imaging can provide a noninvasive method of evaluating in ovo development of smooth muscle tissue.


Subject(s)
Muscle, Smooth/embryology , Animals , Chick Embryo , Diffusion
13.
J Magn Reson Imaging ; 34(2): 318-25, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21780226

ABSTRACT

PURPOSE: To evaluate the role of abdominal susceptibility-weighted imaging (SWI) in the detection of siderotic nodules in cirrhotic liver. MATERIALS AND METHODS: Forty patients with pathologically identified liver cirrhosis and 40 age/sex-matched normal controls underwent T1-, T2-, T2*-weighted imaging and SWI at 3T. Two radiologists prospectively analyzed all magnetic resonance imaging (MRI) studies. Siderotic nodules detected by each imaging technique were counted for comparison. The conspicuity of siderotic nodules was assessed using a scale from 1 to 3 (1, weak; 2, moderate; 3, prominent). RESULTS: The number of siderotic nodules detected by SWI (3863) was significantly greater than that of T1-weighted imaging (262, P < 0.001), T2-weighted imaging (842, P < 0.001), and T2*-weighted imaging (2475, P < 0.001). No suspected siderotic nodules were detected in normal controls by any imaging technique. CONCLUSION: SWI appears to provide the most sensitive method to detect siderotic nodules in cirrhotic liver.


Subject(s)
Image Processing, Computer-Assisted/methods , Liver Cirrhosis/diagnosis , Liver/physiopathology , Magnetic Resonance Imaging/methods , Adult , Aged , Diagnostic Imaging/methods , Female , Humans , Male , Middle Aged , Movement , Respiration , Retrospective Studies
14.
Invest New Drugs ; 26(2): 159-67, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18219445

ABSTRACT

BACKGROUND: ZD6126 is a novel vascular-targeting agent that disrupts the endothelial tubulin cytoskeleton causing selective occlusion of tumor vasculature and extensive tumor necrosis. This Phase I clinical study was conducted to evaluate the dose and administration schedule of ZD6126. METHODS: Adult patients with solid tumors refractory to existing treatments received a 10-min, single-dose intravenous infusion of ZD6126 every 14 or 21 days. Subsequent dose escalation was performed, based on the incidence of adverse events (AEs) within the first cycle of drug administration. Blood samples were obtained for pharmacokinetic analysis, and the effects of ZD6126 on tumor vasculature were visualized using DCE-MRI technology. RESULTS: Forty-four patients received ZD6126 (5-112 mg/m2 in the 21-day schedule, n=35; 40-80 mg/m2 in the 14-day schedule, n=9). Common AEs were similar in both groups and included abdominal pain, nausea and vomiting, which appeared to be dose related. The incidence of abdominal pain at 112 mg/m2 in the 21-day study prevented further dose escalation. Pharmacokinetic studies confirmed that ZD6126 is rapidly hydrolyzed to ZD6126 phenol. There was no difference in the pharmacokinetics of ZD6126 phenol upon repeat administration or between the two dosing regimens. DCE-MRI evaluation has demonstrated the antivascular effects of ZD6126. CONCLUSIONS: This study identified that ZD6126 administered every 2 or 3 weeks at 80 mg/m2 was well tolerated, with mild but manageable gastrointestinal AEs. In approximately 11% (5 out of 44) of patients, ZD6126 was associated with cardiac events categorized as dose limiting toxicities (one patient with asymptomatic decreased left ventricular ejection fraction (LVEF), two with increased troponin concentrations, one with myocardial ischemia, and one with ECG signs of myocardial ischemia).


Subject(s)
Antineoplastic Agents/administration & dosage , Neoplasms/drug therapy , Organophosphorus Compounds/administration & dosage , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Female , Humans , Infusions, Intravenous , Magnetic Resonance Imaging , Male , Middle Aged , Organophosphorus Compounds/adverse effects , Organophosphorus Compounds/pharmacokinetics , Tubulin/drug effects
15.
J Magn Reson Imaging ; 24(1): 41-51, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16755540

ABSTRACT

PURPOSE: To evaluate the diagnostic value of susceptibility-weighted imaging (SWI) for studying brain masses. MATERIALS AND METHODS: SWI is a high-resolution, three-dimensional, fully velocity-compensated gradient-echo sequence that uses both magnitude and phase data. Custom postprocessing is applied to enhance the contrast in the magnitude images between tissues with different susceptibilities. This sequence was applied to 44 patients (24 males and 20 females, 15-89 years old, mean age = 50.3 years) with brain masses, pre- and/or postcontrast, and compared with conventional sequences (T1, T1 postcontrast, T2, proton density (PD), fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) at 1.5T). Correlation with pathology was obtained in 12 cases. All images were reviewed independently by three radiologists. RESULTS: In the evaluation of tumor visibility, boundary definition, blood products, venous vasculature, architecture, and edema, SWI gave better information than the standard T1-weighted postcontrast images in 11%, 14%, 71%, 73%, 63%, and 75% of the data, respectively, in a subgroup of 38 patients. This demonstrates that the information presented by SWI is complementary in nature to that available from conventional methods. On the whole, SWI was much more sensitive for showing blood products and venous vasculature. SWI showed a useful FLAIR-like contrast and complemented the information obtained by conventional T1 postcontrast sequences regarding the internal architecture of the lesions. Good pathologic correlations were found for blood products as predicted by SWI. CONCLUSION: SWI should prove useful for tumor characterization because of its ability to better highlight blood products and venous vasculature and reveal new internal architecture.


Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/pathology , Magnetic Resonance Imaging/methods , Adolescent , Adult , Aged , Aged, 80 and over , Brain Diseases/pathology , Contrast Media/pharmacology , Female , Humans , Male , Middle Aged , Neoplasm Metastasis
16.
J Magn Reson Imaging ; 22(4): 439-50, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16163700

ABSTRACT

Susceptibility-weighted imaging (SWI) consists of using both magnitude and phase images from a high-resolution, three-dimensional, fully velocity compensated gradient-echo sequence. Postprocessing is applied to the magnitude image by means of a phase mask to increase the conspicuity of the veins and other sources of susceptibility effects. This article gives a background of the SWI technique and describes its role in clinical neuroimaging. SWI is currently being tested in a number of centers worldwide as an emerging technique to improve the diagnosis of neurological trauma, brain neoplasms, and neurovascular diseases because of its ability to reveal vascular abnormalities and microbleeds.


Subject(s)
Brain , Magnetic Resonance Imaging/methods , Brain Injuries/diagnosis , Brain Neoplasms/diagnosis , Cerebrovascular Disorders/diagnosis , Contrast Media , Humans , Intracranial Arteriovenous Malformations/diagnosis , Models, Theoretical , Neurodegenerative Diseases/diagnosis
17.
Clin Cancer Res ; 10(11): 3650-7, 2004 Jun 01.
Article in English | MEDLINE | ID: mdl-15173071

ABSTRACT

PURPOSE: ZD6126 is a novel vascular targeting agent currently undergoing clinical evaluation. It acts by destabilizing the microtubulin of fragile and proliferating neoendothelial cells in tumors. The drug leads to blood vessel congestion, the selective destruction of the vasculature, and extensive necrosis in experimental tumors. The aim of the study reported here was to assess the ability of dynamic contrast enhanced magnetic resonance imaging (MRI) to measure the antivascular effects of ZD6126 in tumors. EXPERIMENTAL DESIGN: The work was carried out in mice bearing C38 colon adenocarcinoma and in patients with advanced cancers. MRI was performed before and 6 h (human tumors) or 24 h (C38 tumors) after i.v. drug administration. Contrast agent (gadolinium diethylenetriaminepentaacetate) enhancement was characterized by the initial area under the gadolinium diethylenetriaminepentaacetate uptake versus time curve (IAUC). IAUC reflects blood flow, vascular permeability, and the fraction of interstitial space. RESULTS: The median IAUC was reduced in all C38 tumors after ZD6126 administration [by 6-48% at 50 mg/kg (n = 3)], 58-91% at 100 mg/kg (n = 4), and 11-93% at 200 mg/kg (n = 6). In contrast, the administration of vehicle only led to no consistent change in median IAUC (n = 4). The ZD6126-induced changes in median IAUC appeared to be dose dependent (P = 0.045). No ZD6126-induced changes were apparent in murine muscle. Similar effects were seen in preliminary data from human tumors (11 tumors studied, 9 patients). At doses of 80 mg/m(2) and higher, the median IAUC post-ZD6126 treatment was reduced in all of the tumors studied (8 tumors, 6 patients) to 36-72% from the baseline value. There was a significant trend of increasing reductions with increasing exposure (P < 0.01). No drug-induced changes in human muscle or spleen IAUC were apparent. The reproducibility of the median IAUC parameter was investigated in patients. In 19 human tumors (measured in 19 patients) inter- and intratumor coefficients of variation were 64 and 18%. CONCLUSIONS: The contrast enhanced-MRI measured median IAUC is a useful end point for quantifying ZD6126 antivascular effects in human tumors.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Magnetic Resonance Imaging/methods , Organophosphorus Compounds/pharmacology , Animals , Area Under Curve , Cell Line, Tumor , Cell Proliferation , Contrast Media/pharmacology , Dose-Response Relationship, Drug , Female , Gadolinium DTPA/pharmacology , Humans , Kinetics , Male , Mice , Necrosis , Time Factors , Treatment Outcome
18.
Childs Nerv Syst ; 19(2): 69-81, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12607023

ABSTRACT

OBJECTIVE: The object of this study was to increase our understanding of the social, clinical, radiographic and psychological consequences of child abuse after the initial insult and to describe the role of neurosurgery and other specialties in this context. METHODS: A review of the literature on child abuse (using scientific journals, textbooks, and internet reports) was conducted, with special attention given to child abuse in infants. The biomechanical patterns of injury, the long-term neurological, psychological, and social outcomes and methods of rehabilitation are reviewed. CONCLUSIONS: Head injury associated with physical abuse carries a significantly worse clinical outcome than accidental trauma. Late findings in CT scans and MRI show evidence of cerebral atrophy in 100% and cerebral ischemia in 50% of physical abuse cases. Abuse and neglect have a strong impact in developing children, producing emotional, cognitive, and social problems that may persist throughout the rest of their lives. Outcome cannot be improved without an integrated rehabilitation strategy encompassing early field management, hospital therapy, precise targeting of educational and cognitive needs, and finally return to the community. New ancillary tests have emerged that are aimed at improving rehabilitation and illuminating the long-term physiological and functional impact of abuse.


Subject(s)
Central Nervous System Diseases/physiopathology , Child Abuse , Trauma, Nervous System/physiopathology , Central Nervous System Diseases/psychology , Central Nervous System Diseases/rehabilitation , Child , Child Behavior Disorders/etiology , Child, Preschool , Humans , Infant , Intellectual Disability/etiology , Learning Disabilities/etiology , Memory Disorders/etiology , Outcome Assessment, Health Care , Retinal Hemorrhage/etiology , Trauma, Nervous System/psychology , Trauma, Nervous System/rehabilitation
19.
Neurol Res ; 24 Suppl 1: S17-26, 2002.
Article in English | MEDLINE | ID: mdl-12074432

ABSTRACT

This article presents a review of the current techniques in Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) that enhance the usefulness of these tests for the diagnosis of cerebral disease. We were able to analyze concepts and definitions and give a comparative description for each test studied including Multidetector/Perfusion CT, Xenon CT, CT-Angiogram, MRI-Perfusion, MRI-Diffusion, MRI-Spectroscopy, MRI CSF Flow, Functional MRI studies and Cerebral Angiography.


Subject(s)
Brain Diseases/diagnostic imaging , Magnetic Resonance Imaging , Neuroradiography , Tomography, X-Ray Computed , Cerebral Angiography , Diffusion Magnetic Resonance Imaging , Magnetic Resonance Angiography , Magnetic Resonance Spectroscopy
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