A Phase I Dosing Study of Ferumoxytol for MR Lymphography at 3 T in Patients With Prostate Cancer.

OBJECTIVE: The objective of our study was to determine the optimal dose of ferumoxytol for performing MR lymphography (MRL) at 3 T in patients with prostate cancer. SUBJECTS AND METHODS: This phase I trial enrolled patients undergoing radical prostatectomy (RP) with bilateral pelvic lymph node dissection (PLND). Three groups of five patients each (total of 15 patients) received IV ferumoxytol before RP with bilateral PLND at each of the following doses of iron: 4, 6, and 7.5 mg Fe/kg. Patients underwent abdominopelvic MRI at 3 T before and 24 hours after ferumoxytol injection using T2- and T2*-weighted sequences. Normalized signal intensity (SI) and normalized SD changes from baseline to 24 hours after injection within visible lymph nodes were calculated for each dose level. Linear mixed effects models were used to estimate the effects of dose on the percentage SI change and log-transformed SD change within visible lymph nodes to determine the optimal dose of ferumoxytol for achieving uniform low SI in normal nodes. RESULTS: One patient who was excluded from the study group had a mild allergic reaction requiring treatment after approximately 2.5 mg Fe/kg ferumoxytol injection whereupon the injection was interrupted. The 15 study group patients tolerated ferumoxytol at all dose levels. The mean percentage SI change in 13 patients with no evidence of lymph metastasis was -36.4%, -45.4%, and -65.1% for 4, 6, and 7.5 mg Fe/kg doses, respectively (p = 0.041). CONCLUSION: A dose level of 7.5 mg Fe/kg ferumoxytol was safe and effective in deenhancing benign lymph nodes. This dose therefore can be the starting point for future phase II studies regarding the efficacy of ferumoxytol for MRL.

Magnetic resonance sentinel lymph node imaging of the prostate with gadofosveset trisodium-albumin: preliminary results in a canine model.

RATIONALE AND OBJECTIVES: To determine if intraprostatic injection of gadofosveset trisodium mixed with human serum albumin (HSA) can identify sentinel lymph nodes (LNs) draining the prostate on magnetic resonance imaging (MRI) in a canine model. MATERIALS AND METHODS: Three male canines weighing between 25.7 and 41.3 kg were anesthetized, placed in a 3-T MRI, and a needle was placed transrectally into one side of the prostate using a commercially available intrarectal needle guide. Gadofosveset trisodium premixed with 10% HSA was then administered at doses ranging from 0.1 to 2.5 mL. T1W MRI was performed immediately after injection, and two readers evaluated images for visualization of LNs draining the prostate. RESULTS: Intraprostatic injection of 0.2 mL gadofosveset trisodium premixed with HSA identified the draining periprostatic LNs in all cases. Delayed images demonstrated upper echelon nodes in the pelvis and the abdomen. Higher volume injections resulted in excessive periprostatic extravasation, whereas lower volume injections resulted in suboptimal visualization of LNs. CONCLUSIONS: We demonstrate that gadofosveset trisodium (premixed with 10% HSA) injected intraprostatically at 0.2 mL visualized LNs draining the prostate. This approach can be readily adapted for clinical applications such as sentinel LN imaging in prostate cancer patients before surgery.

Comparison of calculated and acquired high b value diffusion-weighted imaging in prostate cancer.

PURPOSE: To determine whether the performance of calculated high b value diffusion-weighted images (DWI) derived from regular lower b value DWI using exponential diffusion decay models (intravoxel incoherent motion = IVIM and diffusional kurtosis = DK) is comparable to acquired high b value DWI in prostate cancer detection. MATERIALS AND METHODS: One hundred six patients underwent diagnostic multiparametric prostate MRI at 3T using an endorectal coil. Five b value (b = 0, 188, 375, 563, 750 s/mm(2)) DWI and high b value (b = 0, 1000 and 2000 s/mm(2)) DWI were acquired. Calculated high b value (b = 1000 s/mm(2) and b = 2000 s/mm(2)) DWI were derived from the DWI dataset using DK and IVIM models. Calculated and acquired high b value DWI images were compared for lesion visibility and image quality by two experienced radiologists (1 and 6 years of experience). GEE with Wald test was used to compare the image quality among the four calculated high b value DWI by comparing the proportion of lesions in each model which were comparable to the acquired images. This comparison was done for all lesions and by lesion location (PZ or CG; low apical/anterior or apical/mid/base) RESULTS: More lesions were visible on acquired b = 2000 s/mm(2) compared to b = 1000 s/mm(2) DWI. Calculated high b value DWI using the IVIM model had approximately the same number of lesions as acquired high b value DWI, whereas the DK model had fewer lesions than acquired images. The image quality of calculated high b value DWI was comparable to that of acquired images, and the highest quality images were obtained with b1000IVIM. The image quality of calculated b1000IVIM was the same as that of acquired DWI in apical/mid/base (98%) locations and comparable in low apical and anterior (95.4%) locations. The image quality of calculated b2000IVIM was inferior in both apical/mid/base (86.2%) locations and comparable in low apical and anterior (83.9%) locations. CONCLUSION: Calculated high b value DWI obtained using IVIM model has same lesion visibility as that of acquired DWI. The image quality of calculated high b value DWI relative to corresponding acquired DWI decreases with increase in b value.

Natural history of small index lesions suspicious for prostate cancer on multiparametric MRI: recommendations for interval imaging follow-up.

PURPOSE: We aimed to determine the natural history of small index lesions identified on multiparametric-magnetic resonance imaging (MP-MRI) of the prostate by evaluating lesion-specific pathology and growth on serial MP-MRI. MATERIALS AND METHODS: We performed a retrospective review of 153 patients who underwent a minimum of two MP-MRI sessions, on an institutional review board-approved protocol. Index lesion is defined as the lesion(s) with the highest cancer suspicion score based on initial MP-MRI of a patient, irrespective of size. Two study cohorts were identified: (1) patients with no index lesion or index lesion(s) ≤7 mm and (2) a subset with no index lesion or index lesion(s) ≤5 mm. Pathological analysis of the index lesions was performed following magnetic resonance/ultrasound fusion-guided biopsy. Growth rate of the lesions was calculated based on MP-MRI follow-up. RESULTS: Patients with small index lesions measuring ≤7 mm (n=42) or a subset with lesions ≤5 mm (n=20) demonstrated either benign findings (86.2% and 87.5%, respectively) or low grade Gleason 6 prostate cancer (13.8% and 12.5%, respectively) on lesion-specific targeted biopsies. These lesions demonstrated no significant change in size (P = 0.93 and P = 0.36) over a mean imaging period of 2.31±1.56 years and 2.40±1.77 years for ≤7 mm and ≤5 mm index lesion thresholds, respectively. These findings held true on subset analyses of patients who had a minimum of two-year interval follow-up with MP-MRI. CONCLUSION: Small index lesions of the prostate are pathologically benign lesions or occasionally low-grade cancers. Slow growth rate of these small index lesions on serial MP-MRI suggests a surveillance interval of at least two years without significant change.

Role of multiparametric magnetic resonance imaging in the diagnosis of prostate cancer.

Prostate cancer is the most common solid-organ malignancy among American men. It is currently most commonly diagnosed on random systematic biopsies prompted by elevated serum PSA levels. Multi-parametric MRI (MP-MRI) of the prostate has emerged as an anatomic and functional imaging modality, which offers accurate detection, localization and staging of prostate cancer. Recently, MP-MRI has gained an increasing role in guiding biopsies to sites of abnormality and in monitoring patients on active surveillance. Here, we discuss the historical development, current role, and potential future directions of MP-MRI in the diagnosis of prostate cancer.