Asra Khan

Registration methodology for histological sections and in-vivo imaging of human prostate

RATIONALE AND OBJECTIVES Registration enables quantitative spatial correlation of features from different imaging modalities. Our objective is to register in vivo imaging with histologic sections of the human prostate so that histologic truth can be correlated with in vivo imaging features. MATERIALS AND METHODS In vivo imaging of the prostate included T2-weighted anatomic and diffusion weighted 3-T magnetic resonance imaging (MRI) as well as 11C-choline positron emission tomography (PET). In addition, ex vivo 3-T MRI of the prostate specimen, histology, and associated block face photos of the prostate specimen were obtained. A standard registration method based on mutual information (MI) and thin-plate spline (TPS) was applied. Registration among in vivo imaging modalities is well established; however, accurate registration involving histology is difficult. Our approach breaks up the difficult direct registration of histology and in vivo imaging into achievable subregistration tasks involving intermediate ex vivo modalities like block face photography and specimen MRI. Results of subregistration tasks are combined to compute the intended, final registration between in vivo imaging and histology. RESULTS The methodology was applied to two patients and found to be clinically feasible. Overall registered anatomic MRI, diffusion MRI, and 11C-choline PET aligned well with histology qualitatively for both patients. There is no ground truth of registration accuracy as the scans are real patient scans. An indirect validation of the registration accuracy has been proposed comparing tumor boundary markings found in diffusion MRI and histologic sections. Registration errors for two patients between diffusion MRI and histology were 3.74 and 2.26 mm. CONCLUSION This proof of concept paper demonstrates a method based on intrinsic image information content for successfully registering in vivo imaging of the human prostate with its post-resection histology, which does not require the use of extrinsic fiducial markers. The methodology successfully mapped histology onto the in vivo imaging space, allowing the observation of how well different in vivo imaging features correspond to histologic truth. The methodology is therefore the basis for a systematic comparison of in vivo imaging for staging of human prostate cancer.

Detection of Aggressive Primary Prostate Cancer with 11C-Choline PET/CT Using Multimodality Fusion Techniques

The aim of the study was to assess whether 11C-choline PET/CT could identify high-risk primary adenocarcinoma of the prostate. Methods: 11C-choline PET/CT and transpelvic MRI were performed in 14 patients with untreated localized primary adenocarcinoma of the prostate, followed by radical prostatectomy as a form of primary monotherapy within 14 d of in vivo imaging. To allow accurate coregistration of whole-mount histology with in vivo imaging, additional ex vivo MR images of the prostatectomy specimen were obtained. Nonlinear 3-dimensional image deformations were used for registrations of PET/CT, MRI, and histology. Volumes of interest from tumor and benign tissue were defined on the basis of histology and were transferred into coregistered 11C-choline PET/CT volumes to calculate the mean (T(mean)/B) and maximum (T(max)/B) ratio of tumor to benign prostate background. On the basis of MIB-1/Ki-67 expression in tumor tissues represented on a tissue microarray, we assessed whether 11C-choline uptake correlated with local Gleason score and tumor proliferation. Results: Histology confirmed 42 tumor nodules with Gleason scores between 3 + 2 and 4 + 4, with volumes ranging from 0.03 to 12.6 cm3. T(mean)/B (P < 0.01) and T(max)/B (P < 0.001) ratios were significantly increased in high–Gleason score (≥4 + 3) lesions versus 3 + 4 and lower disease but failed to distinguish between 3 + 4 disease versus 3 + 3 and lower. T(mean)/B and T(max)/B ratios were significantly increased in tumors with an MIB-1/Ki-67 labeling index greater than or equal to 5% (P < 0.01). Conclusion: On the basis of our preliminary data using ratios of tumor to benign prostate background, 11C-choline preferentially identified aggressive primary prostate cancer.

Value of delayed hypointensity and delayed enhancing rim in magnetic resonance imaging diagnosis of small hepatocellular carcinoma in the cirrhotic liver

To determine the diagnostic utility of delayed hypointensity and delayed enhancing rim on magnetic resonance imaging (MRI) as indicators of hepatocellular carcinoma (HCC) in arterially enhancing nodules ≤5 cm in the cirrhotic liver and determine the features that best predict HCC.

Possible biliary disease: Diagnostic performance of high-spatial-resolution isotropic 3D T2-weighted MRCP

PURPOSE To retrospectively assess the diagnostic performance of magnetic resonance cholangiopancreatography (MRCP) performed by using a high-spatial-resolution isotropic three-dimensional (3D) fast-recovery fast spin-echo (FSE) sequence with parallel imaging for the evaluation of possible biliary disease. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Ninety-five patients (58 female, 37 male; mean age, 51 years; range, 15-91 years) underwent MRCP by using the respiratory-triggered isotropic 3D fast-recovery FSE sequence and endoscopic or percutaneous direct visualization between March 2003 and June 2007. Two independent readers evaluated the MRCP images for strictures, dilatation, and intraductal filling defects. Sensitivity, specificity, and interobserver agreement (kappa statistics) were determined. RESULTS The respective sensitivity and specificity for strictures, dilatation, and intraductal filling defects (all choledocholithiasis) were 86% (40 of 47) and 94% (45 of 48), 98% (57 of 58) and 100% (37 of 37), and 68% (19 of 28) and 97% (65 of 67) for reader 1 and 88% (41 of 47) and 94% (45 of 48), 96% (56 of 58) and 100% (37 of 37), and 75% (21 of 28) and 99% (66 of 67) for reader 2. The sensitivity for stones larger than 3 mm was 94% (15 of 16) for reader 1 and 100% (16 of 16) for reader 2, whereas the sensitivity for stones 3 mm or smaller was 33% (four of 12) for reader 1 and 42% (five of 12) for reader 2. Agreement between readers was good to excellent, with kappa values of 0.76, 0.85, and 0.98 for strictures, dilatation, and choledocholithiasis, respectively. CONCLUSION MRCP by using the respiratory-triggered isotropic 3D fast-recovery FSE sequence with parallel imaging demonstrates excellent diagnostic capabilities for possible biliary disease, although it is limited for stones 3 mm or smaller in size.

Abdominal applications of diffusion-weighted magnetic resonance imaging: Where do we stand

Diffusion-weighted imaging (DWI) is one of the magnetic resonance imaging (MRI) sequences providing qualitative as well as quantitative information at a cellular level. It has been widely used for various applications in the central nervous system. Over the past decade, various extracranial applications of DWI have been increasingly explored, as it may detect changes even before signal alterations or morphological abnormalities become apparent on other pulse sequences. Initial results from abdominal MRI applications are promising, particularly in oncological settings and for the detection of abscesses. The purpose of this article is to describe the clinically relevant basic concepts of DWI, techniques to perform abdominal DWI, its analysis and applications in abdominal visceral MR imaging, in addition to a brief overview of whole body DWI MRI.

Validation of automatic target volume definition as demonstrated for 11C-choline PET/CT of human prostate cancer using multi-modality fusion techniques.

RATIONALE AND OBJECTIVES Positron emission tomography (PET) is actively investigated to aid in target volume definition for radiation therapy. The objectives of this study were to apply an automatic computer algorithm to compute target volumes and to validate the algorithm using histologic data from real human prostate cancer. MATERIALS AND METHODS Various modalities for prostate imaging were performed. In vivo imaging included T2 3-T magnetic resonance imaging and (11)C-choline PET. Ex vivo imaging included 3-T magnetic resonance imaging, histology, and block face photos of the prostate specimen. A novel registration method based on mutual information and thin-plate splines was applied to all modalities. Once PET is registered with histology, a voxel-by-voxel comparison between PET and histology is possible. A thresholding technique based on various fractions of the maximum standardized uptake value in the tumor was applied, and the respective computed threshold volume on PET was compared with histologic truth. RESULTS Sixteen patients whose primary tumor volumes ranged from 1.2 to 12.6 cm(3) were tested. PET has low spatial resolution, so only tumors > 4 cm(3) were considered. Four cases met this criterion. A threshold value of 60% of the (11)C-choline maximum standardized uptake value resulted in the highest volume overlap between threshold volume on PET and histology. Medial axis distances between threshold volume on PET and histology showed a mean error of 7.7 +/- 5.2 mm. CONCLUSIONS This is a proof-of-concept study demonstrating for the first time that histology-guided thresholding on PET can delineate tumor volumes in real human prostate cancer.

Diagnostic yield of percutaneous image-guided tissue biopsy of focal hepatic lesions in cancer patients: ten percent are not metastases from the primary malignancy.

The diagnostic yield was evaluated of percutaneous image‐guided tissue biopsy of hepatic lesions identified on computed tomography performed for staging of a primary malignancy, and it was determined how often the biopsy result was unexpectedly negative, benign, or secondary to a second unknown malignancy.

False Positive Diagnosis of Metastatic Esophageal Carcinoma on Positron Emission Tomography: A Case Report of Cholecystitis Simulating a Hepatic Lesion

Esophageal cancer has been increasing in incidence for the last several decades. The current staging evaluation includes computed tomography, endoscopic ultrasonography, and F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), which influences the treatment options. PET/CT is limited in its ability to differentiate hypermetabolic metastatic disease from acute/chronic inflammatory conditions, and this must be considered during interpretation. This is the case report of a 77-year-old man with esophageal cancer whose PET/CT demonstrated increased F-18 FDG uptake in the right lobe of the liver. This was originally interpreted at an outside institution as suspicious for metastatic disease, which would have precluded potential surgical cure. Subsequent reinterpretation and additional imaging including magnetic resonance imaging suggested that the uptake in the liver was likely due to adjacent gallbladder inflammation. On the basis of this interpretation, an abdominal exploration, liver biopsy, cholecystectomy, and transhiatal esophagectomy were performed. Final pathology of the gallbladder revealed perforated cholecystitis and a pericholecystic abscess (related to a prior septic episode), which were responsible for the increased radiotracer uptake. This case is presented to illustrate the importance of considering benign etiologies that may mimic metastatic disease when interpreting PET/CT scans.