Free-breathing high-resolution respiratory-gated radial stack-of-stars magnetic resonance imaging of the upper abdomen at 7 T.

Ultrahigh field magnetic resonance imaging (MRI) (≥ 7 T) has the potential to provide superior spatial resolution and unique image contrast. Apart from radiofrequency transmit inhomogeneities in the body at this field strength, imaging of the upper abdomen faces additional challenges associated with motion-induced ghosting artifacts. To address these challenges, the goal of this work was to develop a technique for high-resolution free-breathing upper abdominal MRI at 7 T with a large field of view. Free-breathing 3D gradient-recalled echo (GRE) water-excited radial stack-of-stars data were acquired in seven healthy volunteers (five males/two females, body mass index: 19.6-24.8 kg/m2) at 7 T using an eight-channel transceive array coil. Two volunteers were also examined at 3 T. In each volunteer, the liver and kidney regions were scanned in two separate acquisitions. To homogenize signal excitation, the time-interleaved acquisition of modes (TIAMO) method was used with personalized pairs of B1 shims, based on a 23-s Cartesian fast low angle shot (FLASH) acquisition. Utilizing free-induction decay navigator signals, respiratory-gated images were reconstructed at a spatial resolution of 0.8 × 0.8 × 1.0 mm3. Two experienced radiologists rated the image quality and the impact of B1 inhomogeneity and motion-related artifacts on multipoint scales. The images of all volunteers showcased effective water excitation and were accurately corrected for respiratory motion. The impact of B1 inhomogeneity on image quality was minimal, underscoring the efficacy of the multitransmit TIAMO shim. The high spatial resolution allowed excellent depiction of small structures such as the adrenal glands, the proximal ureter, the diaphragm, and small blood vessels, although some streaking artifacts persisted in liver image data. In direct comparisons with 3 T performed for two volunteers, 7-T acquisitions demonstrated increases in signal-to-noise ratio of 77% and 58%. Overall, this work demonstrates the feasibility of free-breathing MRI in the upper abdomen at submillimeter spatial resolution at a magnetic field strength of 7 T.

Ferumoxtran-10-enhanced MRI for pre-operative metastatic lymph node detection in pancreatic, duodenal, or periampullary adenocarcinoma.

OBJECTIVES: To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology. METHODS: Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs. RESULTS: Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively. CONCLUSION: USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy. REGISTRATION: The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 . KEY POINTS: LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.

Single-spoke binning: Reducing motion artifacts in abdominal radial stack-of-stars imaging.

PURPOSE: To increase the effectiveness of respiratory gating in radial stack-of-stars MRI, particularly when imaging at high spatial resolutions or with multiple echoes. METHODS: Free induction decay (FID) navigators were integrated into a three-dimensional gradient echo radial stack-of-stars pulse sequence. These navigators provided a motion signal with a high temporal resolution, which allowed single-spoke binning (SSB): each spoke at each phase encode step was sorted individually to the corresponding motion state of the respiratory signal. SSB was compared with spoke-angle binning (SAB), in which all phase encode steps of one projection angle were sorted without the use of additional navigator data. To illustrate the benefit of SSB over SAB, images of a motion phantom and of six free-breathing volunteers were reconstructed after motion-gating using either method. Image sharpness was quantitatively compared using image gradient entropies. RESULTS: The proposed method resulted in sharper images of the motion phantom and free-breathing volunteers. Differences in gradient entropy were statistically significant (p = 0.03) in favor of SSB. The increased accuracy of motion-gating led to a decrease of streaking artifacts in motion-gated four-dimensional reconstructions. To consistently estimate respiratory signals from the FID-navigator data, specific types of gradient spoiler waveforms were required. CONCLUSION: SSB allowed high-resolution motion-corrected MR imaging, even when acquiring multiple gradient echo signals or large acquisition matrices, without sacrificing accuracy of motion-gating. SSB thus relieves restrictions on the choice of pulse sequence parameters, enabling the use of motion-gated radial stack-of-stars MRI in a broader domain of clinical applications.

The radiological interpretation of possible microbleeds after moderate or severe traumatic brain injury: a longitudinal study.

INTRODUCTION: In order to augment the certainty of the radiological interpretation of "possible microbleeds" after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI. METHODS: Standardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up. RESULTS: Of the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations. CONCLUSIONS: Our findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.

Post-exercise intramuscular O2 supply is tightly coupled with a higher proximal-to-distal ATP synthesis rate in human tibialis anterior.

KEY POINTS: The post-exercise recovery of phosphocreatine, a measure of the oxidative capacity of muscles, as assessed by 31 P MR spectroscopy, shows a striking increase from distal to proximal along the human tibialis anterior muscle. To investigate why this muscle exhibits a greater oxidative capacity proximally, we tested whether the spatial variation in phosphocreatine recovery rate is related to oxygen supply, muscle fibre type or type of exercise. We revealed that oxygen supply also increases from distal to proximal along the tibialis anterior, and that it strongly correlated with phosphocreatine recovery. Carnosine level, a surrogate measure for muscle fibre type was not different between proximal and distal, and type of exercise did not affect the gradient in phosphocreatine recovery rate. Taken together, the findings of this study suggest that the post-exercise spatial gradients in oxygen supply and phosphocreatine recovery are driven by a higher intrinsic mitochondrial oxidative capacity proximally. ABSTRACT: Phosphorus magnetic resonance spectroscopy (31 P MRS) of human tibialis anterior (TA) revealed a strong proximo-distal gradient in the post-exercise phosphocreatine (PCr) recovery rate constant (kPCr ), a measure of muscle oxidative capacity. The aim of this study was to investigate whether this kPCr gradient is related to O2 supply, resting phosphorylation potential, muscle fibre type, or type of exercise. Fifteen male volunteers performed continuous isometric ankle dorsiflexion at 30% maximum force until exhaustion. At multiple locations along the TA, we measured the oxidative PCr resynthesis rate (VPCr = kPCr × PCr depletion) by 31 P MRS, the oxyhaemoglobin recovery rate constant (kO2Hb ) by near infrared spectroscopy, and muscle perfusion with MR intravoxel incoherent motion imaging. The kO2Hb , kPCr , VPCr and muscle perfusion depended on measurement location (P < 0.001, P < 0.001, P = 0.032 and P = 0.003, respectively), all being greater proximally. The kO2Hb and muscle perfusion correlated with kPCr (r = 0.956 and r = 0.852, respectively) and VPCr (r = 0.932 and r = 0.985, respectively), the latter reflecting metabolic O2 consumption. Resting phosphorylation potential (PCr/inorganic phosphate) was also higher proximally (P < 0.001). The surrogate for fibre type, carnosine content measured by 1 H MRS, did not differ between distal and proximal TA (P = 0.884). Performing intermittent exercise to avoid exercise ischaemia, still led to larger kPCr proximally than distally (P = 0.013). In conclusion, the spatial kPCr gradient is strongly associated with the spatial variation in O2 supply. It cannot be explained by exercise-induced ischaemia nor by fibre type. Our findings suggest it is driven by a higher proximal intrinsic mitochondrial oxidative capacity, apparently to support contractile performance of the TA.

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.

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.

Contribution of Histopathologic Tissue Composition to Quantitative MR Spectroscopy and Diffusion-weighted Imaging of the Prostate.

PURPOSE: To determine associations of metabolite levels derived from magnetic resonance (MR) spectroscopic imaging (ie, hydrogen 1 [(1)H] MR spectroscopic imaging) and apparent diffusion coefficients (ADCs) from diffusion-weighted imaging with prostate tissue composition assessed by digital image analysis of histologic sections. MATERIALS AND METHODS: Institutional ethical review board approved this retrospective study and waived informed consent. Fifty-seven prostate cancer patients underwent an MR examination followed by prostatectomy. One hematoxylin and eosin-stained section of the resected prostate per patient was digitized and computationally segmented into nuclei, lumen, and combination of epithelial cytoplasm and stroma. On each stained section, regions of interest (ROIs) were chosen and matched to the corresponding ADC map and (1)H MR spectroscopic imaging voxels. ADC and two metabolite ratios (citrate [Cit], spermine [Spm], and creatine [Cr] to choline [Cho] and Cho to Cr plus Spm) were correlated with percentage areas of nuclei, lumen, and cytoplasm and stroma for peripheral zone (PZ), transition zone (TZ), and tumor tissue in both zones of the prostate by using a linear mixed-effect model and Spearman correlation coefficient (ρ). RESULTS: ADC and (Cit + Spm + Cr)/Cho ratio showed positive correlation with percentage area of lumen (ρ = 0.43 and 0.50, respectively) and negative correlation with percentage area of nuclei (ρ = -0.29 and -0.26, respectively). The Cho/(Cr + Spm) ratio showed negative association with percentage area of lumen (ρ = -0.40) and positive association with area of nuclei (ρ = 0.26). Percentage areas of lumen and nuclei, (Cit + Spm + Cr)/Cho ratio, and ADC were significantly different (P < .001) between benign PZ (23.7 and 7.7, 8.83, and 1.58 × 10(-3) mm(2)/sec, respectively) and tumor PZ tissue (11.4 and 12.5, 5.13, and 1.20 × 10(-3) mm(2)/sec, respectively). These parameters were also significantly different between benign TZ (20.0 and 8.2, 6.50, and 1.26 × 10(-3) mm(2)/sec, respectively) and tumor TZ tissue (9.8 and 11.2, 4.36, and 1.03 × 10(-3) mm(2)/sec, respectively). CONCLUSION: The observed correlation of (Cit + Spm + Cr)/Cho ratio and ADC of the prostate with its tissue composition indicates that components of this composition, such as percentage luminal area, contribute to the value of these MR parameters.

(1)H MR spectroscopic imaging of the prostate at 7T using spectral-spatial pulses.

PURPOSE: To assess the feasibility of prostate (1)H MR spectroscopic imaging (MRSI) using low-power spectral-spatial (SPSP) pulses at 7T, exploiting accurate spectral selection and spatial selectivity simultaneously. METHODS: A double spin-echo sequence was equipped with SPSP refocusing pulses with a spectral selectivity of 1 ppm. Three-dimensional prostate (1)H-MRSI at 7T was performed with the SPSP-MRSI sequence using an 8-channel transmit array coil and an endorectal receive coil in three patients with prostate cancer and in one healthy subject. No additional water or lipid suppression pulses were used. RESULTS: Prostate (1)H-MRSI could be obtained well within specific absorption rate (SAR) limits in a clinically feasible time (10 min). Next to the common citrate signals, the prostate spectra exhibited high spermine signals concealing creatine and sometimes also choline. Residual lipid signals were observed at the edges of the prostate because of limitations in spectral and spatial selectivity. CONCLUSION: It is possible to perform prostate (1)H-MRSI at 7T with a SPSP-MRSI sequence while using separate transmit and receive coils. This low-SAR MRSI concept provides the opportunity to increase spatial resolution of MRSI within reasonable scan times.

Repeatability of (31) P MRSI in the human brain at 7 T with and without the nuclear Overhauser effect.

An often-employed strategy to enhance signals in (31) P MRS is the generation of the nuclear Overhauser effect (NOE) by saturation of the water resonance. However, NOE allegedly increases the variability of the (31) P data, because variation is reported in NOE enhancements. This would negate the signal-to-noise (SNR) gain it generates. We hypothesized that the variation in NOE enhancement values is not caused by the variability in NOE itself, but is attributable to measurement uncertainties in the values used to calculate the enhancement. If true, the expected increase in SNR with NOE would improve the repeatability of (31) P MRS measurements. To verify this hypothesis, a repeatability study of native and NOE-enhanced (31) P MRSI was performed in the brains of seven healthy volunteers at 7 T. The repeatability coefficient (RC) and the coefficient of variation in repeated measurements (CoVrepeat ) were determined for each method, and the 95% limits of agreement (LoAs) between native and NOE-enhanced signals were calculated. The variation between the methods, defined by the LoA, is at least as great as that predicted by the RC of each method. The sources of variation in NOE enhancements were determined using variance component analysis. In the seven metabolites with a positive NOE enhancement (nine metabolite resonances assessed), CoVrepeat improved, on average, by 15%. The LoAs could be explained by the RCs of the individual methods for the majority of the metabolites, generally confirming our hypothesis. Variation in NOE enhancement was mainly attributable to the factor repeat, but between-voxel effects were also present for phosphoethanolamine and (glycero)phosphocholine. CoVrepeat and fitting error were strongly correlated and improved with positive NOE. Our findings generally indicate that NOE enhances the signal of metabolites, improving the repeatability of metabolite measurements. Additional variability as a result of NOE was minimal. These findings encourage the use of NOE-enhanced (31) P MRSI. Copyright © 2015 John Wiley & Sons, Ltd.

Improved volume selective (1) H MR spectroscopic imaging of the prostate with gradient offset independent adiabaticity pulses at 3 tesla.

PURPOSE: Volume selection in (1) H MR spectroscopic imaging (MRSI) of the prostate is commonly performed with low-bandwidth refocusing pulses. However, their large chemical shift displacement error (CSDE) causes lipid signal contamination in the spectral range of interest. Application of high-bandwidth adiabatic pulses is limited by radiofrequency (RF) power deposition. In this study, we aimed to provide an MRSI sequence that overcomes these limitations. METHODS: Measurements were performed at 3 T with an endorectal receive coil. A semi-LASER sequence was equipped with low RF power demanding gradient-modulated offset-independent adiabaticity (GOIA) refocusing pulses with WURST(16,4) modulation, with a 10 kHz bandwidth. RESULTS: Simulations and phantom studies verified that the GOIA pulses select slices with a flat top and sharp edges and minimal CSDE. The sequence timing was tuned to an optimal citrate signal shape at an echo time of 88 ms. Patient studies (n = 10) demonstrated that high quality spectra with reduced lipid artifacts can be obtained from the whole prostate. Compared with PRESS acquisition at 145 ms the signal-to-noise ratio (SNR) of citrate is increased up to 2.6 and choline up to 1.3. CONCLUSION: An MRSI sequence of the prostate is presented with minimized spectral lipid contamination and improved SNR, to facilitate routine clinical acquisition of metabolic data.

(31) P MR spectroscopic imaging of the human prostate at 7 T: T1 relaxation times, Nuclear Overhauser Effect, and spectral characterization.

PURPOSE: Optimization of phosphorus ((31) P) MR spectroscopic imaging (MRSI) of the human prostate at 7 T by the evaluation of T1 relaxation times and the Nuclear Overhauser Effect (NOE) of phosphorus-containing metabolites. METHODS: Twelve patients with prostate cancer and one healthy volunteer were scanned on a 7 T whole-body system using a (31) P endorectal coil combined with an eight-channel (1) H body array coil. T1 relaxation times were measured using progressive saturation in a two-dimensional localization sequence. (31) P MRSI was performed twice: once without NOE and once with NOE using low-power continuous wave (1) H irradiation to determine NOE enhancements. RESULTS: T1 relaxation times of (31) P metabolites in the human prostate at 7 T varied between 3.0 and 8.3 s. Positive but variable NOE enhancements were measured for most metabolites. Remarkably, the (31) P MR spectra showed two peaks in chemical shift range of inorganic phosphate. CONCLUSION: Knowledge of T1 relaxation times and NOE enhancements enables protocol optimization for (31) P MRSI of the prostate at 7 T. With a strongly reduced (31) P flip angle (≤ 45°), a (31) P MRSI dataset with optimal signal-to-noise ratio per unit time can be obtained within 15 minutes. The NOE enhancement can improve fitting accuracy, but its variability requires further investigation.

Feasibility of T2 -weighted turbo spin echo imaging of the human prostate at 7 tesla.

PURPOSE: To demonstrate that high quality T2 -weighted (T2w) turbo spin-echo (TSE) imaging of the complete prostate can be achieved routinely and within safety limits at 7 T, using an external transceive body array coil only. METHODS: Nine healthy volunteers and 12 prostate cancer patients were scanned on a 7 T whole-body system. Preparation consisted of B0 and radiofrequency shimming and localized flip angle calibration. T1 and T2 relaxation times were measured and used to define the T2w-TSE protocol. T2w imaging was performed using a TSE sequence (pulse repetition time/echo time 3000-3640/71 ms) with prolonged excitation and refocusing pulses to reduce specific absorption rate. RESULTS: High quality T2w TSE imaging was performed in less than 2 min in all subjects. Tumors of patients with gold-standard tumor localization (MR-guided biopsy or prostatectomy) were well visualized on 7 T imaging (n = 3). The number of consecutive slices achievable within a 10-g averaged specific absorption rate limit of 10 W/kg was ≥28 in all subjects, sufficient for full prostate coverage with 3-mm slices in at least one direction. CONCLUSION: High quality T2w TSE prostate imaging can be performed routinely and within specific absorption rate limits at 7 T with an external transceive body array.

Limited Role of the Apparent Diffusion Coefficient (ADC) for Tumor Grade and Overall Survival in Resectable Pancreatic Ductal Adenocarcinoma.

This study evaluated the relationship between apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and tumor grades based on WHO, Adsay, and Kalimuthu classifications, using whole-mount pancreatectomy specimens. If glandular formation plays a key role in the degree of diffusion restriction, diffusion-weighted imaging could facilitate non-invasive grading of PDAC. A freehand region of interest (ROI) was drawn along tumor borders on the preoperative ADC map in each tumor-containing slice. Resection specimens were retrospectively graded according to WHO, Adsay, and Kalimuthu classifications and correlated with overall survival and the 10th percentile of whole-volume ADC values. Findings from 40 patients (23 male, median age 67) showed no correlation between ADC p10 values and WHO differentiation (p = 0.050), Adsay grade (p = 0.955), or Kalimuthu patterns (p = 0.117). There was no association between ADC p10 and overall survival (p = 0.082) and other clinicopathological variables. Survival was significantly lower for poor tumor differentiation (p = 0.046) and non-glandular Kalimuthu patterns (p = 0.016) and there was a trend towards inferior survival for Adsay G3 (p = 0.090) after correction for age, tumor location, and stage. Preoperative ADC measurements for determining PDAC aggressiveness had limited clinical utility, as there was no correlation with histological parameters or overall survival in resectable PDAC.

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.

Immune regulation and blood-brain barrier permeability in cerebral small vessel disease: study protocol of the INflammation and Small Vessel Disease (INSVD) study - a multicentre prospective cohort study.

INTRODUCTION: The INflammation and Small Vessel Disease (INSVD) study aims to investigate whether peripheral inflammation, immune (dys)regulation and blood-brain barrier (BBB) permeability relate to disease progression in cerebral small vessel disease (SVD). This research aims to pinpoint specific components of the immune response in SVD relating to disease progression. This could identify biomarkers of SVD progression, as well as potential therapeutic targets to inform the development and repurposing of drugs to reduce or prevent SVD, cognitive decline and vascular dementia. METHODS AND ANALYSIS: INSVD is a prospective observational multicentre cohort study in individuals with symptomatic SVD. This longitudinal study combines comprehensive immunophenotyping of the peripheral blood immune compartment with advanced neuroimaging markers of SVD and BBB permeability. The main SVD marker of interest is white matter microstructure as determined by diffusion tensor imaging, a valuable marker of disease progression owing to its sensitivity to early alterations to white matter integrity. The research is being conducted in two sites-in the UK (Cambridge) and the Netherlands (Nijmegen)-with each site recruiting 100 participants (total n=200). Participants undergo clinical and cognitive assessments, blood draws, and brain MRI at baseline and 2-year follow-up. ETHICS AND DISSEMINATION: This study received ethical approval from the local ethics boards (UK: East of England-Cambridge Central Research Ethics Committee (REC) ref: 22/EE/00141, Integrated Research Application System (IRAS) ID: 312 747. Netherlands: Medical Research Ethics Committee (MREC) Oost-Nederland, ref: 2022-13623, NL-number: NL80258.091.22). Written informed consent was obtained from all subjects before the study. Any participant-derived benefits resulting from this research, such as new insights into disease mechanisms or possible novel therapies, will be disseminated to study participants, patient groups and members of the public. TRIAL REGISTRATION NUMBER: NCT05746221.

The Hyperintense study: Assessing the effects of induced blood pressure increase and decrease on MRI markers of cerebral small vessel disease: Study rationale and protocol.

Background: Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels. Methods: Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18-55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn (T = 1), when patients have restarted medication (T = 2) and reached target blood pressure and 1 year later (T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling. Discussion: The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.

Utility of T2-weighted MRI texture analysis in assessment of peripheral zone prostate cancer aggressiveness: a single-arm, multicenter study.

T2-weighted (T2W) MRI provides high spatial resolution and tissue-specific contrast, but it is predominantly used for qualitative evaluation of prostate anatomy and anomalies. This retrospective multicenter study evaluated the potential of T2W image-derived textural features for quantitative assessment of peripheral zone prostate cancer (PCa) aggressiveness. A standardized preoperative multiparametric MRI was performed on 87 PCa patients across 6 institutions. T2W intensity and apparent diffusion coefficient (ADC) histogram, and T2W textural features were computed from tumor volumes annotated based on whole-mount histology. Spearman correlations were used to evaluate association between textural features and PCa grade groups (i.e. 1-5). Feature utility in differentiating and classifying low-(grade group 1) vs. intermediate/high-(grade group ≥ 2) aggressive cancers was evaluated using Mann-Whitney U-tests, and a support vector machine classifier employing "hold-one-institution-out" cross-validation scheme, respectively. Textural features indicating image homogeneity and disorder/complexity correlated significantly (p < 0.05) with PCa grade groups. In the intermediate/high-aggressive cancers, textural homogeneity and disorder/complexity were significantly lower and higher, respectively, compared to the low-aggressive cancers. The mean classification accuracy across the centers was highest for the combined ADC and T2W intensity-textural features (84%) compared to ADC histogram (75%), T2W histogram (72%), T2W textural (72%) features alone or T2W histogram and texture (77%), T2W and ADC histogram (79%) combined. Texture analysis of T2W images provides quantitative information or features that are associated with peripheral zone PCa aggressiveness and can augment their classification.

Model of the point spread function of monolithic scintillator PET detectors for perpendicular incidence.

PURPOSE: Previously, we demonstrated the potential of positron emission tomography detectors consisting of monolithic scintillation crystals read out by arrays of solid-state light sensors. We reported detector spatial resolutions of 1.1-1.3 mm full width at half maximum (FWHM) with no degradation for angles of incidence up to 30 degrees, energy resolutions of approximately 11% FWHM, and timing resolutions of approximately 2 ns FWHM, using monolithic LYSO:Ce3+ crystals coupled to avalanche photodiode (APD) arrays. Here we develop, validate, and demonstrate a simple model of the detector point spread function (PSF) of such monolithic scintillator detectors. METHODS: A PSF model was developed that essentially consists of two convolved components, one accounting for the spatial distribution of the energy deposited by annihilation photons within the crystal, and the other for the influences of statistical signal fluctuations and electronic noise. The model was validated through comparison with spatial resolution measurements on a detector consisting of an LYSO:Ce3+ crystal read out by two APD arrays. RESULTS: The model is shown to describe the measured detector spatial response well at the noise levels found in the experiments. In addition, it is demonstrated how the model can be used to correct the measured spatial response for the influence of the finite diameter of the annihilation photon beam used in the experiments, thus obtaining an estimate of the intrinsic detector PSF. CONCLUSIONS: Despite its simplicity, the proposed model is an accurate tool for analyzing the detector PSF of monolithic scintillator detectors and can be used to estimate the intrinsic detector PSF from the measured one.

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.