Phase I study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies.

PURPOSE: A phase I dose escalation study was performed with systemically delivered lyso-thermosensitive liposomal doxorubicin (LTLD). The primary objectives were to determine the safe maximum tolerated dose (MTD), pharmacokinetic properties, and dose-limiting toxicity (DLT) of LTLD during this combination therapy. MATERIALS AND METHODS: Subjects eligible for percutaneous or surgical radiofrequency (RF) ablation with primary (n = 9) or metastatic (n = 15) tumors of the liver, with four or fewer lesions as large as 7 cm in diameter, were included. RF ablation was initiated 15 minutes after starting a 30-minute intravenous LTLD infusion. Dose levels between 20 mg/m(2) and 60 mg/m(2) were evaluated. Magnetic resonance imaging, positron emission tomography, and computed tomography were performed at predetermined intervals before and after treatment until evidence of recurrence was seen, administration of additional antitumor treatment was performed, or a total of 3 years had elapsed. RESULTS: DLT criteria were met at 60 mg/m(2), and the MTD was defined as 50 mg/m(2). RF ablation was performed during the peak of the plasma concentration-time curve in an effort to yield maximal drug deposition. LTLD produced reversible, dose-dependent neutropenia and leukopenia. CONCLUSIONS: LTLD can be safely administered systemically at the MTD (50 mg/m(2)) in combination with RF ablation, with limited and manageable toxicity. Further evaluation of this agent combined with RF ablation is warranted to determine its role in the management of liver tumors.

Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging.

PURPOSE: A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported. MATERIALS AND METHODS: This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy. RESULTS: Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging. CONCLUSIONS: Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.

Documenting the location of systematic transrectal ultrasound-guided prostate biopsies: correlation with multi-parametric MRI.

During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens.

Clinical utility of real-time fusion guidance for biopsy and ablation.

PURPOSE: To show utility, accuracy, and clinical outcomes of electromagnetic tracking and multimodality image fusion for guidance of biopsy and radiofrequency (RF) ablation procedures. MATERIALS AND METHODS: A combination of conventional image guidance (ultrasound[US]/computed tomography [CT]) and a research navigation system was used in 40 patients undergoing biopsy or RF ablation to assist in target localization and needle and electrode placement. The navigation system displays electromagnetically tracked needles and US images relative to a preprocedural CT scan. Additional images (prior positron emission tomography [PET] or magnetic resonance [MR] imaging) can be fused with CT as needed. Needle aiming with and without tracking were compared, the utility of navigation for each procedure was assessed, the system's off-target tracking error for two different registration methods was evaluated, and setup time was recorded. RESULTS: The tracking error could be evaluated in 35 of 40 patients. A basic tracking error of 3.8 mm ± 2.3 was shown using skin fiducial markers for registration. The error improved to 2.7 mm ± 1.6 when using prior internal needle positions as additional fiducial markers. Real-time fusion of US with CT and registration with prior PET and MR imaging were successful and provided clinically relevant guidance information, enabling 19 of the 40 procedures. CONCLUSIONS: The spatial accuracy of the navigation system is sufficient to display clinically relevant image guidance information during biopsy and RF ablation. Breath holding and respiratory gating are effective in minimizing the error associated with tissue motion. In 48% of cases, the navigation system provided information crucial for successful execution of the procedure. Fusion of real-time US with CT or prior diagnostic images may enable procedures that are not feasible with standard, single-modality image guidance.

Real-time sonography with electromagnetic tracking navigation for biopsy of a hepatic neoplasm seen only on arterial phase computed tomography.

This case illustrates the ability of electromagnetic tracking navigation to localize difficult targets in real time during biopsy or ablation of lesions that are only transiently apparent on arterial phase computed tomography and may be unapparent on sonography. Readily available technology enabling multimodality registration to sonography allows for the use of positron emission tomographic, magnetic resonance imaging, and computed tomographic information during sonographically guided procedures and examinations.

D'Amico risk stratification correlates with degree of suspicion of prostate cancer on multiparametric magnetic resonance imaging.

PURPOSE: We determined whether there is a correlation between D'Amico risk stratification and the degree of suspicion of prostate cancer on multiparametric magnetic resonance imaging based on targeted biopsies done with our electromagnetically tracked magnetic resonance imaging/ultrasound fusion platform. MATERIALS AND METHODS: A total of 101 patients underwent 3 Tesla multiparametric magnetic resonance imaging of the prostate, consisting of T2, dynamic contrast enhanced, diffusion weighted and spectroscopy images in cases suspicious for or with a diagnosis of prostate cancer. All prostate magnetic resonance imaging lesions were then identified and graded by the number of positive modalities, including low-2 or fewer, moderate-3 and high-4 showing suspicion on multiparametric magnetic resonance imaging. The biopsy protocol included standard 12-core biopsy, followed by real-time magnetic resonance imaging/ultrasound fusion targeted biopsies of the suspicious magnetic resonance lesions. Cases and lesions were stratified by the D'Amico risk stratification. RESULTS: In this screening population 90.1% of men had a negative digital rectal examination. Mean±SD age was 62.7±8.3 years and median prostate specific antigen was 5.8 ng/ml. Of the cases 54.5% were positive for cancer on protocol biopsy. Chi-square analysis revealed a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification (p<0.0001). Within cluster resampling demonstrated a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification for magnetic resonance targeted core biopsies and magnetic resonance lesions (p<0.01) CONCLUSIONS: Our data support the notion that using multiparametric magnetic resonance prostate imaging one may assess the degree of risk associated with magnetic resonance visible lesions in the prostate.

Documenting the location of prostate biopsies with image fusion.

OBJECTIVE To develop a system that documents the location of transrectal ultrasonography (TRUS)-guided prostate biopsies by fusing them to MRI scans obtained prior to biopsy, as the actual location of prostate biopsies is rarely known. PATIENTS AND METHODS Fifty patients (median age 61) with a median prostate-specific antigen (PSA) of 5.8 ng/ml underwent 3T endorectal coil MRI prior to biopsy. 3D TRUS images were obtained just prior to standard TRUS-guided 12-core sextant biopsies wherein an electromagnetic positioning device was attached to the needle guide and TRUS probe in order to track the position of each needle pass. The 3D-TRUS image documenting the location of each biopsy was fused electronically to the T2-weighted MRI. Each biopsy needle track was marked on the TRUS images and these were then transposed onto the MRI. Each biopsy site was classified pathologically as positive or negative for cancer and the Gleason score was determined. RESULTS The location of all (n= 605) needle biopsy tracks was successfully documented on the T2-weighted (T2W) MRI. Among 50 patients, 20 had 56 positive cores. At the sites of biopsy, T2W signal was considered 'positive' for cancer (i.e. low in signal intensity) in 34 of 56 sites. CONCLUSION It is feasible to document the location of TRUS-guided prostate biopsies on pre-procedure MRI by fusing the pre-procedure TRUS to an endorectal coil MRI using electromagnetic needle tracking. This procedure may be useful in documenting the location of prior biopsies, improving quality control and thereby avoiding under-sampling of the prostate as well as directing subsequent biopsies to regions of the prostate not previously sampled.

Is apparent diffusion coefficient associated with clinical risk scores for prostate cancers that are visible on 3-T MR images?

PURPOSE: To investigate whether apparent diffusion coefficients (ADCs) derived from diffusion-weighted (DW) magnetic resonance (MR) imaging at 3 T correlate with the clinical risk of prostate cancer in patients with tumors that are visible on MR images, with MR imaging/transrectal ultrasonography (US) fusion-guided biopsy as a reference. MATERIALS AND METHODS: Forty-eight consecutive patients (median age, 60 years; median serum prostate-specific antigen value, 6.3 ng/mL) who underwent DW imaging during 3-T MR imaging with an endorectal coil were included in this retrospective institutional review board-approved study, and informed consent was obtained from each patient. Patients underwent targeted MR imaging/transrectal US fusion-guided prostate biopsy. Mean ADCs of cancerous target tumors were correlated with Gleason and D'Amico clinical risk scores. The true risk group rate and predictive value of the mean ADC for classifying a tumor by its D'Amico clinical risk score was determined by using linear discriminant and receiver operating characteristic analyses. RESULTS: A significant negative correlation was found between mean ADCs of tumors in the peripheral zone and their Gleason scores (P = .003; Spearman ρ = -0.60) and D'Amico clinical risk scores (P < .0001; Spearman ρ = -0.69). ADC was found to distinguish tumors in the peripheral zone with intermediate to high clinical risk from those with low clinical risk with a correct classification rate of 0.73. CONCLUSION: There is a significant negative correlation between ADCs and Gleason and D'Amico clinical risk scores. ADCs may therefore be useful in predicting the aggressiveness of prostate cancer. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100667/-/DC1.

Navigation systems for ablation.

Navigation systems, devices, and intraprocedural software are changing the way interventional oncology is practiced. Before the development of precision navigation tools integrated with imaging systems, thermal ablation of hard-to-image lesions was highly dependent on operator experience, spatial skills, and estimation of positron emission tomography-avid or arterial-phase targets. Numerous navigation systems for ablation bring the opportunity for standardization and accuracy that extends the operator's ability to use imaging feedback during procedures. In this report, existing systems and techniques are reviewed and specific clinical applications for ablation are discussed to better define how these novel technologies address specific clinical needs and fit into clinical practice.

Percutaneous ablation of adrenal tumors.

Adrenal tumors comprise a broad spectrum of benign and malignant neoplasms and include functional adrenal adenomas, pheochromocytomas, primary adrenocortical carcinoma, and adrenal metastases. Percutaneous ablative approaches that have been described and used in the treatment of adrenal tumors include percutaneous radiofrequency ablation, cryoablation, microwave ablation, and chemical ablation. Local tumor ablation in the adrenal gland presents unique challenges, secondary to the adrenal gland's unique anatomic and physiological features. The results of clinical series employing percutaneous ablative techniques in the treatment of adrenal tumors are reviewed in this article. Clinical and technical considerations unique to ablation in the adrenal gland are presented, including approaches commonly used in our practices, and risks and potential complications are discussed.

Radiofrequency ablation of metastatic pheochromocytoma.

In the present report on the preliminary safety and effectiveness of radiofrequency (RF) ablation for pheochromocytoma metastases, seven metastases were treated in six patients (mean size, 3.4 cm; range, 2.2-6 cm). alpha- and beta-adrenergic and catecholamine synthesis inhibition and intraprocedural anesthesia monitoring were used. Safety was assessed by recording ablation-related complications. Complete ablation was defined as a lack of enhancement within the ablation zone on follow-up computed tomography. No serious adverse sequelae were observed. Complete ablation was achieved in six of seven metastases (mean follow-up, 12.3 months; range, 2.5-28 months). In conclusion, RF ablation may be safely performed for metastatic pheochromocytoma given careful attention to peri-procedural management.

Radiofrequency ablation of renal tumors.

Radiofrequency ablation (RFA) of renal tumors is a promising technique that plays a unique and increasingly important role in urologic oncology practices. RFA is appealing as a minimally invasive therapy that may be performed on an outpatient basis. It enables treatment of an area 3 to 5 cm in diameter, with relatively low morbidity and mortality rates. Most interventional radiologists (IRs) are familiar with RFA of liver tumors, and several principles and techniques used in the liver may be extrapolated for use in the kidney. However, it is crucial to bear in mind that local tumor ablation in the kidney presents unique challenges, secondary to the kidney's unique anatomic and physiologic features. Clinical and technical considerations, risks, and complications pertaining to RFA of renal tumors are reviewed here, including approaches commonly used in our practice.

Coronary MR angiography at 3T during diastole and systole.

PURPOSE: To investigate the impact of end-systolic imaging on quality of right coronary magnetic resonance angiography (MRA) in comparison to diastolic and to study the effect of RR interval variability on image quality. MATERIALS AND METHODS: The right coronary artery (RCA) of 10 normal volunteers was imaged at 3T using parallel imaging (sensitivity encoding [SENSE]). Navigator-gated three-dimensional (3D) gradient echo was used three times: 1) end-systolic short acquisition (SS): 35-msec window; 2) diastolic short (DS): middiastolic acquisition using 35-msec window; and 3) diastolic long (DL): 75-msec diastolic acquisition window. Vectorcardiogram (VCG) data was used to analyze RR variability. Vessel sharpness, length, and diameter were compared to each other and correlated with RR variability. Blinded qualitative image scores of the images were compared. RESULTS: Quantitative and qualitative parameters were not significantly different and showed no significant correlation with RR variability. CONCLUSION: Imaging the RCA at 3T during the end-systolic rest period using SENSE is possible without significant detrimental effect on image quality. Breaking away from the standard of imaging only during diastole can potentially improve image quality in tachycardic patients or used for simultaneous imaging during both periods in a single scan.

Respiratory biofeedback during CT-guided procedures.

PURPOSE: Respiratory motion can be a complicating factor during image-guided interventions. The ability to reproduce breath-holds may facilitate safer needle-based procedures. The purpose of this study was to evaluate if respiratory biofeedback decreased variability among breath-holds and if the signals from the respiratory bellows belt can be used to measure target motion. MATERIALS AND METHODS: In phase 1 of the study, a respiratory bellows belt was applied to patients before image-guided interventional procedures. Belt stretch from respiratory motion was converted into voltage readings and displayed on a monitor as biofeedback. Patients were asked to perform inspiratory, expiratory, and midcycle breath-holds with and without the biofeedback. The variability in voltage readings between breath-holds with and without biofeedback was compared. In phase 2, the respiratory bellows belt was used during computed tomography (CT)-guided procedures with the patients blinded to the biofeedback. Voltage readings and CT series numbers were recorded as patients were asked to hold their breath during scans. The variability of CT z-axis targets was compared with the variability of voltage readings. RESULTS: A significant decrease in variability was found during expiratory breath-holds (P = .0083) with trends toward significance with midcycle and inspiratory breath-holds. A positive correlation (Kendall tau = 0.5; P = .024) was shown between CT z-axis and belt stretch variability in subjects who received smaller doses of moderate sedation compared with those who received larger doses or general anesthesia. CONCLUSIONS: Biofeedback may help the patient to have a more consistent breath-hold. The belt could decrease the error and unpredictability from craniocaudal motion of targets during image-guided interventions.

Technologies for guidance of radiofrequency ablation in the multimodality interventional suite of the future.

Several new image-guidance tools and devices are being prototyped, investigated, and compared. These tools are introduced and include prototype software for image registration and fusion, thermal modeling, electromagnetic tracking, semiautomated robotic needle guidance, and multimodality imaging. The integration of treatment planning with computed tomography robot systems or electromagnetic needle-tip tracking allows for seamless, iterative, "see-and-treat," patient-specific tumor ablation. Such automation, navigation, and visualization tools could eventually optimize radiofrequency ablation and other needle-based ablation procedures and decrease variability among operators, thus facilitating the translation of novel image-guided therapies. Much of this new technology is in use or will be available to the interventional radiologist in the near future, and this brief introduction will hopefully encourage research in this emerging area.

Use of hydrodissection to prevent nerve and muscular damage during radiofrequency ablation of kidney tumors.

Muscular complications are uncommon but have been reported after radiofrequency (RF) ablation of renal tumors. Ablation of renal lesions near the psoas muscle may result in paresthesia in the distribution of the genitofemoral nerve. The present report describes a case of sensory and muscular dysfunction after RF ablation of a renal lesion lying on top of the psoas muscle that was treated without hydrodissection. To prevent this complication, hydrodissection was effectively used in two other patients during RF ablation of lesions abutting or in close proximity to the psoas muscle.

Intermittent hepatic vein balloon occlusion during radiofrequency ablation in the liver.

The purpose of the study was to assess the feasibility of intermittent hepatic vein balloon occlusion during percutaneous radiofrequency (RF) ablation. Eight non-anticoagulated patients who had primary (n = 2) and metastatic (n = 6) liver tumors with a mean diameter of 4.2 cm (range 2.4-6.5 cm) were treated, resulting in a mean ablation diameter of 6.3 cm (range 4.3-9.3 cm). Six of 9 (67%) of the balloon-occluded hepatic veins were patent. No clinical sequelae of thrombosis were noted. Mean length of follow-up with CT and/or MRI was 12 months. Local tumor control was achieved in 5 of 8 patients. Intermittent hepatic vein balloon occlusion could potentially be a low-risk adjunctive maneuver for thermal ablation therapy in the treatment of large tumors and tumors adjacent to large vessels.

Palliative radiofrequency ablation for recurrent prostate cancer.

Percutaneous radiofrequency ablation (RFA) is a minimally invasive local therapy for cancer. Its efficacy is now becoming well documented in many different organs, including liver, kidney, and lung. The goal of RFA is typically complete eradication of a tumor in lieu of an invasive surgical procedure. However, RFA can also play an important role in the palliative care of cancer patients. Tumors which are surgically unresectable and incompatible for complete ablation present the opportunity for RFA to be used in a new paradigm. Cancer pain runs the gamut from minor discomfort relieved with mild pain medication to unrelenting suffering for the patient, poorly controlled by conventional means. RFA is a tool which can potentially palliate intractable cancer pain. We present here a case in which RFA provided pain relief in a patient with metastatic prostate cancer with pain uncontrolled by conventional methods.