Mukesh G. Harisinghani

Diagnostic Performance of Nanoparticle-Enhanced Magnetic Resonance Imaging in the Diagnosis of Lymph Node Metastases in Patients With Endometrial and Cervical Cancer

PURPOSE Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. METHODS Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients. RESULTS Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25%). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29%*, 99%, 56%, and 96%, and by USPIO criteria (reader 1/reader 2) were 93%/82%* (*P = .008/.004), 97%/97%, 61%/59%, and 100%/99%, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27%*, 94%, 60%, and 79%, and by USPIO criteria (reader 1/reader 2) were 100%/91%* (*P = .031/.06), 94%/87%, 82%/71%, and 100%/96%, respectively. The kappa statistic was 0.93. CONCLUSION Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning.

Imaging guided biopsy of renal masses: indications, accuracy and impact on clinical management.

PURPOSE We evaluated the indications, accuracy and impact of image guided biopsy of focal renal masses. MATERIALS AND METHODS We retrospectively reviewed 79 image guided renal biopsies in 73 patients. Indications, imaging, and histological and clinical features were analyzed. We assumed that nephrectomy, partial nephrectomy or surgical biopsy of suspicious masses would be done when no percutaneous biopsy had been performed. A change in management was defined as surgical to nonsurgical. RESULTS Clinical management was altered due to results in 32 of the 79 biopsies (41%) in cases managed nonoperatively, including positive and negative biopsies in those followed clinically and with imaging. Of 79 biopsies 49 (62%) were diagnosed positive for malignancy, including 15 (31%) that were not and 34 (69%) that were renal cell carcinoma. The histological diagnosis was negative on 25 biopsies (32%) and positive or negative on 74 (94%). All 5 of the 79 false-negative biopsies (6%) were due to insufficient tissue and involved highly suspicious imaging findings that required further evaluation, such as repeat biopsy or surgery. Renal cell carcinoma was identified in 4 of the 5 cases. In 12 of the 24 patients (50%) with a pre-biopsy history of nonrenal cancer biopsies were diagnostic of nonrenal cancer. No patient had major complications and in 4 small hematomas were treated with observation only. CONCLUSIONS Image guided renal mass biopsy is safe, reliable and accurate, and it changes clinical management in many cases by avoiding nephrectomy or other surgical options. Radiologists should promote imaging guided biopsy as a potentially useful option for managing suspicious or indeterminate renal masses.

Focal Therapy in Prostate Cancer—Report from a Consensus Panel

PURPOSE To establish a consensus in relation to case selection, conduct of therapy, and outcomes that are associated with focal therapy for men with localized prostate cancer. MATERIAL AND METHODS Urologic surgeons, radiation oncologists, radiologists, and histopathologists from North America and Europe participated in a consensus workshop on focal therapy for prostate cancer. The consensus process was face to face within a structured meeting, in which pertinent clinical issues were raised, discussed, and agreement sought. Where no agreement was possible, this was acknowledged, and the nature of the disagreement noted. RESULTS Candidates for focal treatment should have unilateral low- to intermediate-risk disease with clinical stage <or=cT(2a). Prostate size and both tumor volume and tumor topography are important case selection criteria that depend on the ablative technology used. Currently, the best method to ascertain the key characteristics for men who are considering focal therapy is exposure to transperineal template mapping biopsies. MRI of the prostate using novel techniques such as dynamic contrast enhancement and diffusion weighed imaging are increasingly being used to diagnose and stage primary prostate cancer with excellent results. For general use, however, these new techniques require validation in prospective clinical trials. Until such are performed, MRI will, in most centers, continue to be an investigative tool in assessing eligibility of patients for focal therapy. CONCLUSIONS Consensus was derived for most of the key aspects of case selection, conduct of treatment, and outcome measures for men who are undergoing focal therapy for localized prostate cancer. The level of agreement achieved will pave the way for future collaborative trials.

Overview of Dynamic Contrast-Enhanced MRI in Prostate Cancer Diagnosis and Management

OBJECTIVE This article is a primer on the technical aspects of performing a high-quality dynamic contrast-enhanced MRI (DCE-MRI) examination of the prostate gland. CONCLUSION DCE-MRI is emerging as a useful clinical technique as part of a multi-parametric approach for evaluating the extent of primary and recurrent prostate cancer. Performing a high-quality DCE-MRI examination requires a good understanding of the technical aspects and limitations of image acquisition and postprocessing techniques.

Prospective Evaluation of MR Enterography as the Primary Imaging Modality for Pediatric Crohn Disease Assessment

OBJECTIVE The objectives of this study were prospective evaluation of MR enterographic accuracy for detecting Crohn disease imaging features in pediatric patients, compared with a CT reference standard, as well as determination of MR enterographic accuracy for detecting active bowel inflammation and fibrosis using a histologic reference standard. SUBJECTS AND METHODS The study group for this blinded prospective study included 21 pediatric subjects with known Crohn disease scheduled for clinical CT and histologic bowel sampling for symptomatic exacerbation. All subjects and their parents gave informed consent to also undergo MR enterography. CT and MR enterography examinations were independently reviewed by two radiologists and were scored for Crohn disease features. All bowel histology specimens were reviewed by a single pathologist for the presence of active mucosal inflammation and mural fibrosis, followed by correlation of imaging and histologic findings. RESULTS All 21 subjects underwent MR enterography and histologic sampling, 18 of whom also underwent CT. MR enterography had high sensitivity for detecting Crohn disease imaging features (e.g., bowel wall thickening, mesenteric inflammation, lymphadenopathy, fistula, and abscess) compared with CT, with individual sensitivity values ranging from 85.1% to 100%. Of a total of 53 abnormal bowel segments with correlation of MRI and histologic findings, MR enterography showed 86.7% accuracy (90.0% sensitivity and 82.6% specificity) for detecting active inflammation (p < 0.001). The accuracy of MR enterography for detecting mural fibrosis overall was 64.9%, compared with histology, but increased to 83.3% (p < 0.05) for detecting fibrosis without superimposed active inflammation. CONCLUSION MR enterography can substitute for CT as the first-line imaging modality in pediatric patients with Crohn disease, on the basis of its ability to detect intestinal pathologic abnormalities in both small and large bowel as well as extraintestinal disease manifestations. Additionally, MR enterography provides an accurate noninvasive assessment of Crohn disease activity and mural fibrosis and can aid in formulating treatment strategies for symptomatic patients and assessing therapy response.

Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization?

OBJECTIVE Ferumoxtran-10 is a lymphotropic MR contrast agent that is currently under investigation. It has been shown to be effective in staging lymph nodes of patients with various primary malignancies. The current technique with ferumoxtran-10 involves imaging before and 24 hr after contrast administration. The purpose of this study was to evaluate the accuracy of ferumoxtran-10-enhanced images alone in characterizing lymph nodes for oncologic staging 24 hr after contrast enhancement. MATERIALS AND METHODS Seventy-seven patients (58 men, 19 women) with proven primary cancer (bladder [n = 20], breast [n = 10], endometrial [n = 1], renal [n = 3], penile [n = 4], prostate [n = 31], rectal [n = 1], testicular [n = 5], and ureteral [n = 2]) who were scheduled for surgical lymph node dissection were enrolled in the study. In these patients, 169 lymph nodes (mean size, 11.2 mm) were evaluated on T2*-weighted gradient-refocused echo MRI at l.5 T both before and 24-36 hr after the IV administration of ferumoxtran-10 (2.6 mg Fe/kg). Two blinded reviewers with differing levels of interpreting experience separately performed qualitative image evaluation. A 6-point scale was used to characterize lymph nodes on contrast-enhanced images alone and on combined unenhanced and contrast-enhanced images. Receiver operating characteristic (ROC) analysis was performed separately for both reviewers. RESULTS Of the 169 lymph nodes evaluated, 55 were benign and 114 malignant by histopathologic analysis. The results of the ROC analysis comparing contrast-enhanced images ([A(z) = area under ROC curve] reviewer 1, A(z) = 0.92; reviewer 2, A(z) = 0.94) alone with combined unenhanced and contrast-enhanced images (reviewer 1, A(z) = 0.94; reviewer 2, A(z) = 0.93) showed a statistically significant difference (p = 0.01) for reviewer 1 but no difference for reviewer 2 (p = 0.88). Reviewer 2 was more experienced in interpreting ferumoxtran-10-enhanced images than reviewer 1. CONCLUSION On ferumoxtran-10-enhanced MR lymphangiography, contrast-enhanced images alone may suffice for lymph node characterization. However, a certain level of interpretation experience may be required before contrast-enhanced images can be used alone.

Sensitive, Noninvasive Detection of Lymph Node Metastases

Background Many primary malignancies spread via lymphatic dissemination, and accurate staging therefore still relies on surgical exploration. The purpose of this study was to explore the possibility of semiautomated noninvasive nodal cancer staging using a nanoparticle-enhanced lymphotropic magnetic resonance imaging (LMRI) technique. Methods and Findings We measured magnetic tissue parameters of cancer metastases and normal unmatched lymph nodes by noninvasive LMRI using a learning dataset consisting of 97 histologically proven nodes. We then prospectively tested the accuracy of these parameters against 216 histologically validated lymph nodes from 34 patients with primary cancers, in semiautomated fashion. We found unique magnetic tissue parameters that accurately distinguished metastatic from normal nodes with an overall sensitivity of 98% and specificity of 92%. The parameters could be applied to datasets in a semiautomated fashion and be used for three-dimensional reconstruction of complete nodal anatomy for different primary cancers. Conclusion These results suggest for the first time the feasibility of semiautomated nodal cancer staging by noninvasive imaging.

Lymphotropic nanoparticle-enhanced magnetic resonance imaging (LNMRI) identifies occult lymph node metastases in prostate cancer patients prior to salvage radiation therapy ☆

Twenty-six patients with prostate cancer status post-radical prostatectomy who were candidates for salvage radiation therapy (SRT) underwent lymphotropic nanoparticle enhanced MRI (LNMRI) using superparamagnetic nanoparticle ferumoxtran-10. LNMRI was well tolerated, with only two adverse events, both Grade 2. Six (23%) of the 26 patients, previously believed to be node negative, tested lymph node positive by LNMRI. A total of nine positive lymph nodes were identified in these six patients, none of which were enlarged based on size criteria.

Pilot study evaluating use of lymphotrophic nanoparticle-enhanced magnetic resonance imaging for assessing lymph nodes in renal cell cancer.

OBJECTIVE To assess lymphotrophic nanoparticle-enhanced magnetic resonance imaging (LNMRI) in identifying malignant nodal involvement in patients with renal neoplasms. METHODS MRI was performed in 9 patients with renal masses. All patients were imaged on a GE 1.5T system with phased array body coil. Protocols included T2 and T2* weighted imaging before and after administration of ferumoxtran-10 (Combidex) for the evaluation of lymph node (LN) involvement. All 9 patients underwent nephrectomy. Lymph node dissection (LND) was performed in patients with stage 2 renal cell cancer (RCC), or transitional cell cancer (TCC), per routine clinical practice. Data analysis was performed by 2 radiologists, who were blinded to pathologic results. Nodes that lacked contrast uptake were deemed malignant, and those with homogeneous uptake were deemed benign. Quantitative, retrospective analysis was performed on primary tumors by quantifying T2* with a monoexponential fitting algorithm (Osirix). T2* was quantified before, immediately after, and 24 hours after the administration of ferumoxtran-10. RESULTS MRI demonstrated 26 lymph nodes within the 9 patients imaged (24 benign and 2 malignant). Pathologic results allowed comparison in 22 of the 26 lymph nodes and demonstrated high sensitivity (100%) and specificity (95.7%). CONCLUSIONS LNMRI demonstrated high sensitivity (100%) and specificity (95.7%) in patients with renal neoplasms. Although in a relatively small sample size, the results are encouraging and warrant a larger, prospective trial.

Fine-Needle Aspiration Biopsy of Thyroid Nodules: Experience in a Cohort of 944 Patients

OBJECTIVE The objective of our study was to determine the likelihood of malignancy in thyroid nodules and the risk of a nondiagnostic fine-needle aspiration biopsy (FNAB) on the basis of the demographic characteristics of the patients and sonographic features of the nodules. MATERIALS AND METHODS Between January 2002 and November 2007, 2,338 ultrasound-guided thyroid, thyroid bed, and cervical lymph node FNABs were performed at a tertiary referral center. Entry criteria for our retrospective study were adult patients who underwent thyroid nodule FNAB and had previously undergone diagnostic sonography. From previous reports for 944 thyroid nodules (739 nodules in women and 205 nodules in men), four sonographic features were recorded: longest dimension, morphology, presence of microcalcifications, and presence of lymphadenopathy. The final diagnosis of each nodule was classified as benign, malignant, or nondiagnostic on the basis of surgical pathology when available and cytology otherwise and was analyzed for correlation with individual sonographic features and combinations of features. RESULTS The prevalence of malignancy and of nondiagnostic FNAB in this study was 11.0% and 11.8%, respectively. Statistically significant (p < 0.05) findings in malignant nodules were younger patient age (< or = 45 years; odds ratio [OR], 1.54) and solid nodule morphology (OR, 2.38). The significant predictors of a nondiagnostic-quality FNAB were older patient age (> 75 years; OR, 1.95) and a nodule > or = 10 mm (OR, 1.45). Adding information about the other evaluated ultrasound features did not lead to a significant result. CONCLUSION Malignant thyroid nodules tend to be solid (86.5%). Patients older than 75 years showed a clearly increased risk of nondiagnostic FNAB, but to predict a higher risk of malignancy or of nondiagnostic FNAB using ultrasound remains difficult.