The Potential of Iron Oxide Nanoparticle-Enhanced MRI at 7 T Compared With 3 T for Detecting Small Suspicious Lymph Nodes in Patients With Prostate Cancer.

BACKGROUND: Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs. PURPOSE: The aim of this study was to explore USPIO-enhanced MRI at 7 T in comparison to 3 T for the detection of small suspicious LNs in the same cohort of patients with PCa. MATERIALS AND METHODS: Twenty PCa patients with high-risk primary or recurrent disease were referred to our hospital for an investigational USPIO-enhanced 3 T MRI examination with ferumoxtran-10. With consent, they underwent a 7 T MRI on the same day. Three-dimensional anatomical and T2*-weighted images of both examinations were evaluated blinded, with an interval, by 2 readers who annotated LNs suspicious for metastases. Number, size, and level of suspicion (LoS) of LNs were paired within patients and compared between field strengths. RESULTS: At 7 T, both readers annotated significantly more LNs compared with 3 T (474 and 284 vs 344 and 162), with 116 suspicious LNs on 7 T (range, 1-34 per patient) and 79 suspicious LNs on 3 T (range, 1-14 per patient) in 17 patients. For suspicious LNs, the median short axis diameter was 2.6 mm on 7 T (1.3-9.5 mm) and 2.8 mm for 3 T (1.7-10.4 mm, P = 0.05), with large overlap in short axis of annotated LNs between LoS groups. At 7 T, significantly more suspicious LNs had a short axis <2.5 mm compared with 3 T (44% vs 27%). Magnetic resonance imaging at 7 T provided better image quality and structure delineation and a higher LoS score for suspicious nodes. CONCLUSIONS: In the same cohort of patients with PCa, more and more small LNs were detected on 7 T USPIO-enhanced MRI compared with 3 T MRI. Suspicious LNs are generally very small, and increased nodal size was not a good indication of suspicion for the presence of metastases. The high spatial resolution of USPIO-enhanced MRI at 7 T improves structure delineation and the visibility of very small suspicious LNs, potentially expanding the in vivo detection limits of pelvic LN metastases in PCa patients.

Validation of In Vivo Nodal Assessment of Solid Malignancies with USPIO-Enhanced MRI: A Workflow Protocol.

BACKGROUND: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented, which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. METHODS: In patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious of harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. RESULTS: Matching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology, which allowed for analyses on a nodal, or at least on a nodal station, basis. CONCLUSIONS: A workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed for the analysis at a nodal basis, or at least nodal station basis, of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced, MRI-detected lymph nodes.

USPIO-enhanced MRI of lymph nodes in rectal cancer: A node-to-node comparison with histopathology.

PURPOSE: To evaluate the initial results of predicting lymph node metastasis in rectal cancer patients detected in-vivo with USPIO-enhanced MRI at 3 T compared on a node-to-node basis with histopathology. METHODS: Ten rectal cancer patients of all clinical stages were prospectively included for an in-vivo 0.85 mm3 isotropic 3D MRI after infusion of Ferumoxtran-10. The surgical specimens were examined ex-vivo with an 0.29 mm3 isotropic MRI examination. Two radiologists evaluated in-vivo MR images with a classification scheme to predict lymph node status. Ex-vivo MRI was used for MR-guided pathology and served as a key link between in-vivo MRI and final histopathology for the node-to-node analysis. RESULTS: 138 lymph nodes were detected by reader 1 and 255 by reader 2 (p = 0.005) on in-vivo MRI with a median size of 2.6 and 2.4 mm, respectively. Lymph nodes were classified with substantial inter-reader agreement (κ = 0.73). Node-to-node comparison was possible for 55 lymph nodes (median size 3.2 mm; range 1.2-12.3), of which 6 were metastatic on pathology. Low true-positive rates (3/26, 11 % for both readers) and high true negative rates were achieved (14/17, 82 %; 19/22, 86 %). Pathological re-evaluations of 20 lymph nodes with high signal intensity on USPIO-enhanced MRI without lymph node metastases (false positives) did not reveal tumor metastasis but showed benign lymph node tissue with reactive follicles. CONCLUSIONS: High resolution MRI visualizes a large number of mesorectal lymph nodes. USPIO-enhanced MRI was not accurate for characterizing small benign versus small tumoral lymph nodes in rectal cancer patients. Suspicious nodes on in-vivo MRI occur as inflammatory as well as metastatic nodes.

Magnetic resonance imaging at ultra-high magnetic field strength: An in vivo assessment of number, size and distribution of pelvic lymph nodes.

OBJECTIVE: The definition of an in vivo nodal anatomical baseline is crucial for validation of representative lymph node dissections and accompanying pathology reports of pelvic cancers, as well as for assessing a potential therapeutic effect of extended lymph node dissections. Therefore the number, size and distribution of lymph nodes in the pelvis were assessed with high-resolution, large field-of-view, 7 Tesla (T) magnetic resonance imaging (MRI) with frequency-selective excitation. MATERIALS AND METHODS: We used 7 T MRI for homogeneous pelvic imaging in 11 young healthy volunteers. Frequency-selective imaging of water and lipids was performed to detect nodal structures in the pelvis. Number and size of detected nodes was measured and size distribution per region was assessed. An average volunteer-normalized nodal size distribution was determined. RESULTS: In total, 564 lymph nodes were detected in six pelvic regions. Mean number was 51.3 with a wide range of 19-91 lymph nodes per volunteer. Mean diameter was 2.3 mm with a range of 1 to 7 mm. 69% Was 2 mm or smaller. The overall size distribution was very similar to the average volunteer-normalized nodal size distribution. CONCLUSIONS: The amount of in vivo visible lymph nodes varies largely between subjects, whereas the normalized size distribution of nodes does not. The presence of many small lymph nodes (≤2mm) renders representative or complete removal of pelvic lymph nodes to be very difficult. 7T MRI may shift the in vivo detection limits of lymph node metastases in the future.

A multitransmit external body array combined with a 1 H and 31 P endorectal coil to enable a multiparametric and multimetabolic MRI examination of the prostate at 7T.

PURPOSE: In vivo 1 H and 31 P magnetic resonance spectroscopic imaging (MRSI) provide complementary information on the biology of prostate cancer. In this work we demonstrate the feasibility of performing multiparametric imaging (mpMRI) and 1 H and 31 P spectroscopic imaging of the prostate using a 31 P and 1 H endorectal radiofrequency coil (ERC) in combination with a multitransmit body array at 7 Tesla (T). METHODS: An ERC with a 31 P transceiver loop coil and 1 H receive (Rx) asymmetric microstrip (31 P/1 H ERC) was designed, constructed and tested in combination with an external 8-channel 1 H transceiver body array coil (8CH). Electromagnetic field simulations and measurements and in vivo temperature measurements of the ERC were performed for safety validation. In addition, the signal-to-noise (SNR) benefit of the 1 H microstrip with respect to the 8CH was evaluated. Finally, the feasibility of the setup was tested in one volunteer and three patients with prostate cancer by performing T2 -weighted and diffusion-weighted imaging in combination with 1 H and 31 P spectroscopic imaging. RESULTS: Electromagnetic field simulations of the 31 P loop coil showed no differences in the E- and B-fields of the 31 P/1 H ERC compared with a previously safety validated ERC without 1 H microstrip. The hotspot of the specific absorption rate (SAR) at the feed point of the 31 P/1 H ERC loop coil was 9.42 W/kg when transmitting on 31 P at 1 W. Additional in vivo measurements showed a maximum temperature increase at the SAR hotspot of 0.7°C over 6 min on 31 P at 1.9 W transmit (Tx) power, indicating safe maximum power levels. When transmitting with the external 1 H body array at 40W for 2:30 min, the temperature increase around the ERC was < 0.3°C. Up to 3.5 cm into the prostate the 1 H microstrip of the ERC provided higher SNR than the 8CH. The total coil combination allowed acquisition of an mpMRI protocol and the assessment of 31 P and 1 H metabolites of the prostate in all test subjects. CONCLUSION: We developed a setup with a 31 P transceiver and 1 H Rx endorectal coil in combination with an 8-channel transceiver external body array coil and demonstrated its safety and feasibility for obtaining multiparametric imaging and 1 H and 31 P MRSI at 7T in patients with prostate cancer within one MR examination.

Can Ex Vivo Magnetic Resonance Imaging of Rectal Cancer Specimens Improve the Mesorectal Lymph Node Yield for Pathological Examination?

PURPOSE: The aim of this study was to use 7 T ex vivo magnetic resonance imaging (MRI) scans to determine the size of lymph nodes (LNs) in total mesorectal excision (TME) specimens and to increase the pathological yield of LNs with MR-guided pathology. MATERIALS AND METHODS: Twenty-two fixated TME specimens containing adenocarcinoma were scanned on a 7 T preclinical MRI system with a T1-weighted 3-dimensional gradient echo sequence with frequency-selective lipid excitation (repetition time/echo time, 15/3 milliseconds; resolution, 0.293 mm) and a water-excited 3-dimensional multigradient echo (repetition time, 30 milliseconds; computed echo time, 6.2 milliseconds; resolution, 0.293 mm) pulse sequence.The first series of 11 TME specimens (S1) revealed the number and size of LNs on both ex vivo MRI and histopathology. The second series of 11 TME specimens (S2) was used to perform MR-guided pathology. The number, size, and percentages of yielded LNs of S1 and S2 were compared. RESULTS: In all specimens (22/22), a median number of 34 LNs (interquartile range, 26-34) was revealed on ex vivo MRI compared with 14 LNs (interquartile range, 7.5-21.5) on histopathology (P = 0.003). Mean size of all LNs did not differ between the 2 series (ex vivo MRI: 2.4 vs 2.5 mm, P = 0.267; pathology: 3.6 vs 3.5 mm, P = 0.653). The median percentages of harvested LNs compared with nodes visible on ex vivo MRI per specimen for both series were not significantly different (40% vs 43%, P = 0.718). By using a size threshold of greater than 2 mm, the percentage improved to 71% (S1) and to 78% (S2, P = 0.895). The median number of harvested LNs per specimen did not increase by performing MR-guided pathology (S1, 14 LNs; S2, 20 LNs; P = 0.532). CONCLUSIONS: Ex vivo MRI visualizes more LNs than (MR-guided) pathology is able to harvest. Current pathological examination was not further improved by MR guidance. The majority of LNs or LN-like structures visible on ex vivo MRI below 2 mm in size remain unexplained, which warrants a 3-dimensional approach for pathological reconstruction of specimens.

USPIO-enhanced MRI of pelvic lymph nodes at 7-T: preliminary experience.

PURPOSE: To evaluate the technical feasibility of high-resolution USPIO-enhanced magnetic resonance imaging of pelvic lymph nodes (LNs) at ultrahigh magnetic field strength. MATERIALS AND METHODS: The ethics review board approved this study and written informed consent was obtained from all patients. Three patients with rectal cancer and three selected patients with (recurrent) prostate cancer were examined at 7-T 24-36 h after intravenous ferumoxtran-10 administration; rectal cancer patients also received a 3-T MRI. Pelvic LN imaging was performed using the TIAMO technique in combination with water-selective multi-GRE imaging and lipid-selective GRE imaging with a spatial resolution of 0.66 × 0.66 × 0.66mm3. T2*-weighted images of the water-selective imaging were computed from the multi-GRE images at TE = 0, 8, and 14 ms and used for the assessment of USPIO uptake. RESULTS: High-resolution 7-T MR gradient-echo imaging was obtained robustly in all patients without suffering from RF-related signal voids. USPIO signal decay in LNs was visualized using computed TE imaging at TE = 8 ms and an R2* map derived from water-selective imaging. Anatomically, LNs were identified on a combined reading of computed TE = 0 ms images from water-selective scans and images from lipid-selective scans. A range of 3-48 LNs without USPIO signal decay was found per patient. These LNs showed high signal intensity on computed TE = 8 and 14 ms imaging and low R2* (corresponding to high T2*) values on the R2* map. CONCLUSION: USPIO-enhanced MRI of the pelvis at 7-T is technically feasible and offers opportunities for detecting USPIO uptake in normal-sized LNs, due to its high intrinsic signal-to-noise ratio and spatial resolution. KEY POINTS: • USPIO-enhanced MRI at 7-T can indicate USPIO uptake in lymph nodes based on computed TE images. • Our method promises a high spatial resolution for pelvic lymph node imaging.

Effect of lactate administration on brain lactate levels during hypoglycemia in patients with type 1 diabetes.

Administration of lactate during hypoglycemia suppresses symptoms and counterregulatory responses, as seen in patients with type 1 diabetes and impaired awareness of hypoglycemia (IAH), presumably because lactate can substitute for glucose as a brain fuel. Here, we examined whether lactate administration, in a dose sufficient to impair awareness of hypoglycemia, affects brain lactate levels in patients with normal awareness of hypoglycemia (NAH). Patients with NAH (n = 6) underwent two euglycemic-hypoglycemic clamps (2.8 mmol/L), once with sodium lactate infusion (NAH w|lac) and once with saline infusion (NAH w|placebo). Results were compared to those obtained during lactate administration in patients with IAH (n = 7) (IAH w|lac). Brain lactate levels were determined continuously with J-difference editing 1H-MRS. During lactate infusion, symptom and adrenaline responses to hypoglycemia were considerably suppressed in NAH. Infusion of lactate increased brain lactate levels modestly, but comparably, in both groups (mean increase in NAH w|lac: 0.12 ± 0.05 µmol/g and in IAH w|lac: 0.06 ± 0.04 µmol/g). The modest increase in brain lactate may suggest that the excess of lactate is immediately metabolized by the brain, which in turn may explain the suppressive effects of lactate on awareness of hypoglycemia observed in patients with NAH.

7T ultra-high field body MR imaging with an 8-channel transmit/32-channel receive radiofrequency coil array.

PURPOSE: In this work, a combined body coil array with eight transmit/receive (Tx/Rx) meander elements and with 24 receive-only (Rx) loops (8Tx/32Rx) was developed and evaluated in comparison with an 8-channel transmit/receive body array (8Tx/Rx) based on meander elements serving as the reference standard. METHODS: Systematic evaluation of the RF array was performed on a body-sized phantom. Body imaging at 7T was performed in six volunteers in the body regions pelvis, abdomen, and heart. Coil characteristics such as signal-to-noise ratio, acceleration capability, g-factors, S-parameters, noise correlation, and B1+ maps were assessed. Safety was ensured by numerical simulations using a coil model validated by dosimetric field measurements. RESULTS: Meander elements and loops are intrinsically well decoupled with a maximum coupling value of -20.5 dB. Safe use of the 8Tx/32Rx array could be demonstrated. High gain in signal-to-noise ratio (33% in the subject's center) could be shown for the 8Tx/32Rx array compared to the 8Tx/Rx array. Improvement in acceleration capability in all investigations could be demonstrated. For example, the 8Tx/32Rx array provides lower g-factors in the right-left and anterior-posterior directions with R = 3 undersampling as compared to the 8Tx/Rx array using R = 2. Both arrays are very similar regarding their RF transmit performance. Excellent image quality in the investigated body regions could be achieved with the 8Tx/32Rx array. CONCLUSION: In this work, we show that a combination of eight meander elements and 24 loop receive elements is possible without impeding transmit performance. Improved SNR and g-factor performance compared to an RF array without these loops is demonstrated. Body MRI at 7T with the 8Tx/32Rx array could be accomplished in the heart, abdomen, and pelvis with excellent image quality.

Automatic frequency and phase alignment of in vivo J-difference-edited MR spectra by frequency domain correlation.

OBJECTIVE: J-difference editing is often used to select resonances of compounds with coupled spins in 1H-MR spectra. Accurate phase and frequency alignment prior to subtracting J-difference-edited MR spectra is important to avoid artefactual contributions to the edited resonance. MATERIALS AND METHODS: In-vivo J-difference-edited MR spectra were aligned by maximizing the normalized scalar product between two spectra (i.e., the correlation over a spectral region). The performance of our correlation method was compared with alignment by spectral registration and by alignment of the highest point in two spectra. The correlation method was tested at different SNR levels and for a broad range of phase and frequency shifts. RESULTS: In-vivo application of the proposed correlation method showed reduced subtraction errors and increased fit reliability in difference spectra as compared with conventional peak alignment. The correlation method and the spectral registration method generally performed equally well. However, better alignment using the correlation method was obtained for spectra with a low SNR (down to ~2) and for relatively large frequency shifts. CONCLUSION: Our correlation method for simultaneously phase and frequency alignment is able to correct both small and large phase and frequency drifts and also performs well at low SNR levels.

Flexible proton 3D MR spectroscopic imaging of the prostate with low-power adiabatic pulses for volume selection and spiral readout.

PURPOSE: Cartesian k-space sampling in three-dimensional magnetic resonance spectroscopic imaging (MRSI) of the prostate limits the selection of voxel size and acquisition time. Therefore, large prostates are often scanned at reduced spatial resolutions to stay within clinically acceptable measurement times. Here we present a semilocalized adiabatic selective refocusing (sLASER) sequence with gradient-modulated offset-independent adiabatic (GOIA) refocusing pulses and spiral k-space acquisition (GOIA-sLASER-Spiral) for fast prostate MRSI with enhanced resolution and extended matrix sizes. METHODS: MR was performed at 3 tesla with an endorectal receive coil. GOIA-sLASER-Spiral at an echo time (TE) of 90 ms was compared to a point-resolved spectroscopy sequence (PRESS) with weighted, elliptical phase encoding at an TE of 145 ms using simulations and measurements of phantoms and patients (n = 9). RESULTS: GOIA-sLASER-Spiral acquisition allows prostate MR spectra to be obtained in ∼5 min with a quality comparable to those acquired with a common Cartesian PRESS protocol in ∼9 min, or at an enhanced spatial resolution showing more precise tissue allocation of metabolites. Extended field of views (FOVs) and matrix sizes for large prostates are possible without compromising spatial resolution or measurement time. CONCLUSION: The flexibility of spiral sampling enables prostate MRSI with a wide range of resolutions and FOVs without undesirable increases in acquisition times, as in Cartesian encoding. This approach is suitable for routine clinical exams of prostate metabolites. Magn Reson Med 77:928-935, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

High resolution MR imaging of pelvic lymph nodes at 7 Tesla.

PURPOSE: Pelvic lymph node (PLN) metastases are often smaller than 5 mm and difficult to detect. This work presents a method to perform PLN imaging with ultrahigh-field MRI, using spectrally selective excitation to acquire water and lipid-selective imaging at high spatial resolution. METHODS: A 3D water-selective multigradient echo (mGRE) sequence and lipid-selective gradient echo (GRE) sequence were tested in six healthy volunteers on a 7 Tesla (T) MRI system, using time interleaved acquisition of modes (TIAMO) to improve image homogeneity. The size distribution of the first 10 iliac PLNs detected in each volunteer was determined, and the contrast-to-noise ratio (CNR) of these lymph nodes (LNs) was compared with the individual mGRE images, sum-of-squares echo addition, and computed T2*-weighted images derived from the T2* fits. RESULTS: LN imaging was acquired robustly at ultrahigh field with high resolution and homogeneous lipid or water-selective contrast. PLNs down to 1.5-mm short axis were detected with mean ± standard error of the mean (SEM) short and long axes of 2.2 ± 0.1 and 3.7 ± 0.2 mm, respectively. Computed T2*-weighted imaging allowed flexibility in T2* contrast while featuring a CNR up to 90% of the sum-of-squares echo addition. CONCLUSION: Ultrahigh-field MRI in combination with TIAMO and frequency-selective excitation enables high-resolution, large field-of-view MRI of the lower abdomen, and may ultimately be suitable for detecting small PLN metastases. Magn Reson Med 78:1020-1028, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Feasibility of Multiparametric Magnetic Resonance Imaging of the Prostate at 7 T.

OBJECTIVES: The aim of this study was to evaluate the technical feasibility of prostate multiparametric magnetic resonance imaging (mpMRI) at a magnetic field strength of 7 T. MATERIALS AND METHODS: In this prospective institutional review board-approved study, 14 patients with biopsy-proven prostate cancer (mean age, 65.2 years; median prostate-specific antigen [PSA], 6.2 ng/mL), all providing signed informed consent, underwent 7 T mpMRI with an external 8-channel body-array transmit coil and an endorectal receive coil between September 2013 and October 2014. Image and spectral quality of high-resolution T2-weighted (T2W) imaging (0.3 × 0.3 × 2 mm), diffusion-weighted imaging (DWI; 1.4 × 1.4 × 2 mm or 1.75 × 1.75 × 2 mm), and (H) MR spectroscopic imaging (MRSI; real voxel size, 0.6 mm in 7:16 minutes) were rated on a 5-point scale by 2 radiologists and a spectroscopist. RESULTS: Prostate mpMRI including at least 2 of 3 MR techniques was obtained at 7 T in 13 patients in 65 ± 12 minutes. Overall T2W and DWI image quality at 7 T was scored as fair (38% and 17%, respectively) to good or very good (55% and 83%, respectively). The main artifacts for T2W imaging were motion and areas of low signal-to-noise ratio, the latter possibly caused by radiofrequency field inhomogeneities. For DWI, the primary artifact was ghosting of the rectal wall in the readout direction. Magnetic resonance spectroscopic imaging quality was rated fair or good in 56% of the acquisitions and was mainly limited by lipid contamination. CONCLUSIONS: Multiparametric MRI of the prostate at 7 T is feasible at unprecedented spatial resolutions for T2W imaging and DWI and within clinically acceptable acquisition times for high-resolution MRSI, using the combination of an external 8-channel body-array transmit coil and an endorectal receive coil. The higher spatial resolutions can yield improved delineation of prostate anatomy, but the robustness of the techniques needs to be improved before clinical adoption of 7 T mpMRI.