Comparative validation of automated presurgical tractography based on constrained spherical deconvolution and diffusion tensor imaging with direct electrical stimulation.

OBJECTIVES: Accurate presurgical brain mapping enables preoperative risk assessment and intraoperative guidance. This cross-sectional study investigated whether constrained spherical deconvolution (CSD) methods were more accurate than diffusion tensor imaging (DTI)-based methods for presurgical white matter mapping using intraoperative direct electrical stimulation (DES) as the ground truth. METHODS: Five different tractography methods were compared (three DTI-based and two CSD-based) in 22 preoperative neurosurgical patients undergoing surgery with DES mapping. The corticospinal tract (CST, N = 20) and arcuate fasciculus (AF, N = 7) bundles were reconstructed, then minimum distances between tractograms and DES coordinates were compared between tractography methods. Receiver-operating characteristic (ROC) curves were used for both bundles. For the CST, binary agreement, linear modeling, and posthoc testing were used to compare tractography methods while correcting for relative lesion and bundle volumes. RESULTS: Distance measures between 154 positive (functional response, pDES) and negative (no response, nDES) coordinates, and 134 tractograms resulted in 860 data points. Higher agreement was found between pDES coordinates and CSD-based compared to DTI-based tractograms. ROC curves showed overall higher sensitivity at shorter distance cutoffs for CSD (8.5 mm) compared to DTI (14.5 mm). CSD-based CST tractograms showed significantly higher agreement with pDES, which was confirmed by linear modeling and posthoc tests (PFWE < .05). CONCLUSIONS: CSD-based CST tractograms were more accurate than DTI-based ones when validated using DES-based assessment of motor and sensory function. This demonstrates the potential benefits of structural mapping using CSD in clinical practice.

Intra-individual qualitative and quantitative comparison of [68Ga]Ga-DOTATATE PET/CT and PET/MRI.

Background: Somatostatin receptor (SSTR) positron emission tomography (PET) is a cornerstone of neuroendocrine tumor (NET) management. Hybrid PET/magnetic resonance imaging (MRI) is now available for NET-imaging, next to PET/computed tomography (CT). Objectives: To determine whether CT or MRI is the best hybrid partner for [68Ga]Ga-DOTATATE PET. Design: Monocentric, prospective study. Methods: Patients received a same-day [68Ga]Ga-DOTATATE PET/CT and subsequent PET/MRI, for suspicion of NET, (re)staging or peptide receptor radionuclide therapy-selection. The union (PETunion) of malignant lesions detected on PETCT and PETMRI was the reference standard. Concordance of detection of malignant lesions in an organ was measured between PETunion and CT and PETunion and MRI. Seven bins were used to categorize the number of malignant lesions, containing following ordinal variables: 0, 1, 2-5, 6-10, 11-20, >20 countable and diffuse/uncountable. The difference in number of malignant lesions was obtained as the difference in bin level ('Δbin') between PETunion and CT and PETunion and MRI with a Δbin closer to zero implying a higher concordance rate. Results: Twenty-nine patients were included. Primary tumors included 17 gastroenteropancreatic-NETs, 1 colon neuroendocrine carcinoma, 7 lung-NETs and 2 meningiomas. Patient level concordance with PETunion was 96% for MRI and 67% for CT (p = 0.039). Organ level concordance with PETunion was 74% for MRI and 40% for CT (p < 0.0001). In bone, there was a higher concordance rate for MRI compared to CT, 92% and 33%, respectively (p = 0.016). Overall, a mean Δbin of 0.5 ± 1.1 for PETunion/MRI and 1.4 ± 1.2 for PETunion/CT (p < 0.0001) was noted. In liver, a mean Δbin of 0.0 ± 1.1 for PETunion/MRI and 1.7 ± 1.2 for PETunion/CT was observed (p = 0.0078). In bone, a mean Δbin closer to zero was observed for PETunion/MRI compared to PETunion/CT, 0.6 ± 1.4 and 2.0 ± 1.5, respectively (p = 0.0098). Conclusions: Compared to SSTR PET/CT, SSTR PET/MRI had a higher patient and organ level concordance for malignant tumoral involvement and number of malignant lesions, with a clear added value in bone and liver specifically.

Adjustable shunts and proton therapy: a magnetic combination.

OBJECTIVE: Due to evidence for proton beam therapy (PBT) in pediatric central nervous system (CNS) tumors, compact proton therapy systems became commercially available to allow better integration in a hospital setting. However, these systems have a non-zero magnetic field at the level of the patient. Often, these patients have a cerebrospinal fluid shunt, and most of them are adjustable through a magnet. Whether the induced magnetic fields could interfere with adjustable shunts is unknown. METHODS: In the first five CNS tumor patients with adjustable shunts who underwent PBT, the shunt setting was controlled before, during, and after treatment with PBT. Additionally, we used an ex vivo adjustable shunt to check if the settings could be altered by the magnetic field. RESULTS: We did not observe unintentional changes in shunt settings in vivo during treatment. In ex vivo testing, the shunt settings were altered directly cranial to the exit window of PBT due to the magnetic field. CONCLUSION: Although we did not observe any shunt setting alteration during PBT in this small cohort, caution is warranted. Given the lack of high-volume data, there should be a low threshold for checking the shunt setting at the end of PBT therapy or in a symptomatic patient.

Histopathological correlations and fat replacement imaging patterns in recessive limb-girdle muscular dystrophy type 12.

BACKGROUND: Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12). Furthermore, although it is known that LGMDR12 leads to a selective muscle involvement distinct from other muscular dystrophies, the spatial distribution of fat replacement within these muscles is unknown. METHODS: We included 27 adult patients with LGMDR12 and 27 age-matched and sex-matched healthy controls and acquired 6-point Dixon images of the thighs and T1 and short tau inversion recovery (STIR) MR images of the whole body. In 16 patients and 15 controls, we performed three muscle biopsies, one in the semimembranosus, vastus lateralis, and rectus femoris muscles, which are severely, intermediately, and mildly affected in LGMDR12, respectively. We correlated the PDFF to the fat percentage measured on biopsies of the corresponding muscles, as well as to the Rochester histopathology grading scale. RESULTS: In patients, we demonstrated a strong correlation of PDFF on MRI and muscle biopsy fat percentage for the semimembranosus (r = 0.85, P < 0.001) and vastus lateralis (r = 0.68, P = 0.005). We found similar results for the correlation between PDFF and the Rochester histopathology grading scale. Out of the five patients with inflammatory changes on muscle biopsy, three showed STIR hyperintensities in the corresponding muscle on MRI. By modelling the PDFF on MRI for 18 thigh muscles from origin to insertion, we observed a significantly inhomogeneous proximo-distal distribution of fat replacement in all thigh muscles of patients with LGMDR12 (P < 0.001), and different patterns of fat replacement within each of the muscles. CONCLUSIONS: We showed a strong correlation of fat fraction on MRI and fat percentage on muscle biopsy for diseased muscles and validated the use of Dixon fat fraction imaging as an outcome measure in LGMDR12. The inhomogeneous fat replacement within thigh muscles on imaging underlines the risk of analysing only samples of muscles instead of the entire muscles, which has important implications for clinical trials.

Development and characterization of a rat brain metastatic tumor model by multiparametric magnetic resonance imaging and histomorphology.

To facilitate the development of new brain metastasis (BM) treatment, an easy-to-use and clinically relevant animal model with imaging platform is needed. Rhabdomyosarcoma BM was induced in WAG/Rij rats. Post-implantation surveillance and characterizations were systematically performed with multiparametric MRI including 3D T1 and T2 weighted imaging, diffusion-weighted imaging (DWI), T1 and T2 mapping, and perfusion-weighted imaging (PWI), which were validated by postmortem digital radiography (DR), µCT angiography and histopathology. The translational potential was exemplified by the application of a vascular disrupting agent (VDA). BM was successfully induced in most rats of both genders (18/20). Multiparametric MRI revealed significantly higher T2 value, pre-contrast-enhanced (preCE) T1 value, DWI-derived apparent diffusion coefficient (ADC) and CE ratio, but a lower post-contrast-enhanced (postCE) T1 value in BM lesions than in adjacent brain (p < 0.01). PWI showed the dynamic and higher contrast agent uptake in the BM compared with the adjacent brain. DR, µCT and histopathology characterized the BM as hypervascular tumors. After VDA treatment, the BM showed drug-related perfusion changes and partial necrosis as evidenced by anatomical, functional MRI parameters and postmortem findings. The present BM model and imaging modalities represent a feasible and translational platform for developing BM-targeting therapeutics.

Effects of spinal cord stimulation on voxel-based brain morphometry in patients with failed back surgery syndrome.

OBJECTIVE: Despite the clinical effectiveness of Spinal Cord Stimulation (SCS), potential structural brain modifications have not been explored. Our aim was to identify structural volumetric changes during subsensory SCS, in patients with Failed Back Surgery Syndrome (FBSS). METHODS: In this cohort study, twenty-two FBSS patients underwent a magnetic resonance imaging protocol before SCS and 3 months after SCS. Clinical parameters were correlated with volumetric changes, calculated with voxel-based morphometry. RESULTS: After 3 months, a significant volume decrease was found in the inferior frontal gyrus, precuneus, cerebellar posterior lobe and middle temporal gyrus. Significant increases were found in the inferior temporal gyrus, precentral gyrus and the middle frontal gyrus after SCS. Additionally, significant increases in volume of superior frontal and parietal white matter and a significant decrease in volume of white matter underlying the premotor/middle frontal gyrus were revealed after SCS. A significant correlation was highlighted between white matter volume underlying premotor/middle frontal gyrus and leg pain relief. CONCLUSIONS: This study revealed for the first time that SCS is able to induce volumetric changes in gray and white matter, suggesting the reversibility of brain alterations after chronic pain treatment. SIGNIFICANCE: Volumetric brain alterations are observable after 3 months of subsensory SCS in FBSS patients.

A Regions of Interest Voxel-Based Morphometry Study of the Human Brain During High-Frequency Spinal Cord Stimulation in Patients With Failed Back Surgery Syndrome.

INTRODUCTION: The effectiveness of spinal cord stimulation (SCS) as pain-relieving treatment for failed back surgery syndrome (FBSS) has already been demonstrated. However, potential structural and functional brain alterations resulting from subsensory SCS are less clear. The aim of this study was to test structural volumetric changes in a priori chosen regions of interest related to chronic pain after 1 month and 3 months of high-frequency SCS in patients with FBSS. METHODS: Eleven patients with FBSS who were scheduled for SCS device implantation were included in this study. All patients underwent a magnetic resonance imaging protocol before SCS device implantation 1 and 3 months after high-frequency SCS. Pain intensity, pain catastrophizing, and sleep quality were also measured. Regions-of-interest voxel-based morphometry was used to explore grey matter volumetric changes over time. Additionally, volumetric changes were correlated with changes in pain intensity, catastrophizing, and sleep quality. RESULTS: Significant decreases were found in volume in the left and right hippocampus over time. More specifically, a significant difference was revealed between volumes before SCS implantation and after 3 months of SCS. Repeated-measures correlations revealed a significant positive correlation between volumetric changes in the left hippocampus and changes in back pain score over time and between volumetric changes in the right hippocampus and changes in back pain score over time. CONCLUSION: In patients with FBSS, high-frequency SCS influences structural brain regions over time. The volume of the hippocampus was decreased bilaterally after 3 months of high-frequency SCS with a positive correlation with back pain intensity.

Magnetic Resonance Imaging Exploration of the Human Brain During 10 kHz Spinal Cord Stimulation for Failed Back Surgery Syndrome: A Resting State Functional Magnetic Resonance Imaging Study.

INTRODUCTION: Apart from the clinical efficacy of high frequency spinal cord stimulation at 10 kHz, the underlying mechanism of action remains unclear. In parallel with spinal or segmental theories, supraspinal hypotheses have been recently proposed. In order to unveil hidden altered brain connectome patterns, a resting state functional magnetic resonance imaging (rsfMRI) protocol was performed in subjects routinely treated for back and/or leg pain with high-frequency spinal cord stimulation (HF-SCS) HF-SCS at 10 kHz. METHODS: RsfMRI imaging was obtained from ten patients with failed back surgery syndrome who were eligible for HF-SCS at 10 kHz. Specifically-chosen regions of interest with different connectivity networks have been investigated over time. Baseline measurements were compared with measurements after 1 month and 3 months of HF-SCS at 10 kHz. Additionally, clinical parameters on pain intensity, central sensitization, pain catastrophizing, and sleep quality were correlated with the functional connectivity strengths. RESULTS: The study results demonstrate an increased connectivity over time between the anterior insula (affective salience network) and regions of the frontoparietal network and the central executive network. After 3 months of HF-SCS, the increased strength in functional connectivity between the left dorsolateral prefrontal cortex and the right anterior insula was significantly correlated with the minimum clinically important difference (MCID) value of the Pittsburgh sleep quality index. CONCLUSION: These findings support the hypothesis that HF-SCS at 10 kHz might influence the salience network and therefore also the emotional awareness of pain.

Functional magnetic resonance imaging: cerebral function alterations in subthreshold and suprathreshold spinal cord stimulation.

BACKGROUND AND PURPOSE: Failed back surgery syndrome (FBSS) is a common and devastating chronic neuropathic pain disorder. Conventional spinal cord stimulation (SCS) applies electrical suprathreshold pulses to the spinal cord at a frequency of 40-60 Hz and relieves pain in FBSS patients. During the last decade, two major changes have emerged in the techniques of stimulating the spinal cord: paresthesia-free or subthreshold stimulation and administration of higher frequency or higher amounts of energy to the spinal cord. Despite the positive clinical results, the mechanism of action remains unclear. A functional MRI (fMRI) study was conducted to investigate the brain alterations during subthreshold and suprathreshold stimulation at different frequencies. METHODS: Ten subjects with FBSS, treated with externalized SCS, received randomly four different stimulation frequencies (4 Hz, 60 Hz, 500 Hz, and 1 kHz) during four consecutive days. At every frequency, the patient underwent sub- and suprathreshold stimulation. Cerebral activity was monitored and assessed using fMRI. RESULTS: Suprathreshold stimulation is generally accompanied with more activity than sub-threshold SCS. Suprathreshold SCS resulted in increased bilateral activation of the frontal cortex, thalamus, pre- and postcentral gyri, basal ganglia, cingulate gyrus, insula, thalamus, and claustrum. We observed deactivation of the bilateral parahippocampus, amygdala, precuneus, posterior cingulate gyrus, postcentral gyrus, and unilateral superior temporal gyrus. CONCLUSION: Suprathreshold stimulation resulted in greater activity (both activation and deactivation) of the frontal brain regions; the sensory, limbic, and motor cortices; and the diencephalon in comparison with subthreshold stimulation. Each type of frequency at suprathreshold stimulation was characterized by an individual activation pattern.

Advanced MR diffusion imaging and chemotherapy-related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

With the increase of survival rates of pediatric cancer patients, the number of children facing potential cognitive sequelae has grown. Previous adult studies suggest that white matter (WM) microstructural changes may contribute to cognitive impairment. This study aims to investigate WM microstructure in childhood bone and soft tissue sarcoma. Differences in (micro-)structure can be investigated using diffusion MRI (dMRI). The typically used diffusion tensor model (DTI) assumes Gaussian diffusion, and lacks information about fiber populations. In this study, we compare WM structure of childhood bone and soft tissue sarcoma survivors (n = 34) and matched controls (n = 34), combining typical and advanced voxel-based models (DTI and NODDI model, respectively), as well as recently developed fixel-based models (for estimations of intra-voxel differences, apparent fiber density [AFD] and fiber cross-section [FC]). Parameters with significant findings were compared between treatments, and correlated with subscales of the WAIS-IV intelligence test, age at diagnosis, age at assessment and time since diagnosis. We encountered extensive regions showing lower fractional anisotropy, overlapping with both significant NODDI parameters and fixel-based parameters. In contrast to these diffuse differences, the fixel-based measure of AFD was reduced in the cingulum and corpus callosum only. Furthermore, AFD of the corpus callosum was significantly predicted by chemotherapy treatment and correlated positively with time since diagnosis, visual puzzles and similarities task scores. This study suggests altered WM structure of childhood bone and soft tissue sarcoma survivors. We conclude global chemotherapy-related changes, with particular vulnerability of centrally located WM bundles. Finally, such differences could potentially recover after treatment.

Characterization of a novel liquid fiducial marker for multimodal image guidance in stereotactic body radiotherapy of prostate cancer.

PURPOSE: Liquid fiducial markers have shown to be a promising alternative to solid gold markers in terms of imaging artifact reduction, patient comfort, and compatibility with different imaging modalities. This study aims to investigate the performance of the novel BioXmark® liquid marker for state-of-the-art multimodal imaging used in prostate cancer (PCa) radiotherapy, encompassing kV CT/CBCT, multiparametric MRI, and kV x-ray imaging. In addition, automatic detection of the liquid markers in x-ray imaging for prostate motion monitoring during treatment was investigated. METHODS: A total of eight BioXmark® liquid markers with varying volumes (range 5-300 µL) were casted on a square grid into a gelatin phantom insert. A cylindrical gold marker (QLRAD, length = 7 mm, Ø = 1 mm) was inserted for reference. Liquid marker visibility and streaking artifacts in CT/CBCT imaging were evaluated by placing the gelatin phantom into a CIRS anthropomorphic phantom. Relevant MRI characteristics such as the T2 and T1 relaxation times, the ADC value, and the relative proton density (ρH) were quantified by placing the gelatin phantom insert next to a T1MES mapping phantom and a water-filled syringe for reference. Ex vivo multiparametric MRI images were acquired by placing the gelatin phantom next to a resected prostate specimen. Anterior-posterior x-ray projection images were obtained by placing the gelatin phantom insert on top of an anthropomorphic pelvic phantom with internal pelvic bony structures and were acquired for five positions relative to the bony anatomy and 24 clinically relevant x-ray exposure settings. To quantify individual automatic marker detection, single markers were artificially isolated in the x-ray images using postprocessing. RESULTS: Markers of all sizes were clearly visible on CT and CBCT images with only the largest marker volumes (100-300 µL) displaying artifacts similar in size to the gold fiducial marker. Artifact size increased with increasing liquid marker volume. Liquid markers displayed good contrast in ex vivo T1-weighted and ρH-weighted images. The markers were not visible in the ex vivo T2-weighted image. The liquid markers induced a chemical shift artifact in the obtained ADC-map. Automated detection in x-ray imaging was feasible with high detection success (four of five positions) for marker volumes in the range of 25-200 µL. None of the liquid markers were detected successfully when superimposed on a bony edge, independent of their size. CONCLUSIONS: This study is the first to show the compatibility of BioXmark® liquid markers with multimodal image-guided radiotherapy for PCa. Compared to a solid gold marker, they had favorable results in both visibility and induced imaging artifacts. Liquid marker visibility in MRI imaging of the prostate does not solely depend on the low ρH value (not visible on T2-weighted image) but is also influenced by its relaxation times. Automated marker detection in x-ray images was feasible but better adapted marker detection algorithms are necessary for marker localization in the presence of bony edges. Hence, the liquid marker provides a minimally invasive (fine needles) and highly applicable alternative to current solid gold markers for multimodal image-guided prostate radiotherapy treatments.

Recovery from chemotherapy-induced white matter changes in young breast cancer survivors?

In a previous longitudinal diffusion tensor imaging (DTI) study, we observed cerebral white matter (WM) alterations (reduced fractional anisotropy (FA)) related to decreased cognitive performance 3-5 months after chemotherapy-treatment (t2) when compared to baseline (t1) (Deprez et al. in Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30(3), 274-281. doi:10.1200/JCO.2011.36.8571, 2012). The current study investigates the evolution and the nature of these previously observed microstructural changes. Twenty-five young women with early-stage breast cancer who received chemotherapy treatment (C+), 14 who did not receive chemotherapy (C-) and 15 healthy controls (HC) previously studied, underwent reassessment 3-4 years after treatment (t3). We assessed (1) longitudinal changes of cognitive performance and FA and (2) cross-sectional group differences in myelin-water-imaging and multishell diffusion MRI metrics at t3. MRI metrics were assessed on a voxel-by-voxel basis and in regions-of-interest (ROI) in which previous WM injury was detected. Longitudinal results: Mixed-effects modeling revealed significant group-time interactions for verbal memory and processing speed (p < 0.05) reflecting regained performance in the C+ group at t3. Furthermore, in chemotherapy-treated patients, FA returned to baseline levels at t3 in all ROIs (p < 0.002), whereas no FA changes were seen in controls. Additionally, FA increase from t2 to t3 correlated with time since treatment in two of the four regions (r = 0.40, p < 0.05). Cross-sectional results: Advanced diffusion MRI and myelin-water imaging metrics in the ROIs did not differ between groups. Similarly, no whole-brain voxelwise differences were detected. Initial WM alterations and reduced cognitive performance following chemotherapy-treatment were found to recover in a group of young breast cancer survivors three to four years after treatment.

Pancreatic imaging: Current status of clinical practices and small animal studies.

Different causative factors acting on the pancreas can result in diseases such as pancreatitis, diabetes and pancreatic tumors. The high incidence and mortality of pancreatic diseases have placed diagnostic imaging in a crucial position in daily clinical practice. In this mini-review article different pancreatic imaging techniques are discussed, from the standard clinical imaging modalities and state of the art clinical magnetic resonance imaging techniques to current situations in pre-clinical pancreatic imaging studies. In particular, the challenges of pre-clinical rodent pancreatic imaging are addressed, with both the image acquisition techniques and the post-processing methods for rodent pancreatic imaging elaborated.

Brain responses to vestibular pain and its anticipation in women with Genito-Pelvic Pain/Penetration Disorder.

OBJECTIVE: In DSM-5, pain-related fear during anticipation of vaginal penetration is a diagnostic criterion of Genito-Pelvic Pain/Penetration Disorder (GPPPD). We aimed to investigate subjective and brain responses during anticipatory fear and subsequent induction of vestibular pain in women with GPPPD. METHODS: Women with GPPPD (n = 18) and age-matched healthy controls (HC) (n = 15) underwent fMRI scanning during vestibular pain induction at individually titrated pain threshold after a cued anticipation period. (Pain-related) fear and anxiety traits were measured with questionnaires prior to scanning, and anticipatory fear and pain intensity were rated during scanning using visual analog scales. RESULTS: Women with GPPPD reported significantly higher levels of anticipatory fear and pain intensity. During anticipation and pain induction they had stronger and more extensive brain responses in regions involved in cognitive and affective aspects of pain perception, but the group difference did not reach significance for the anticipation condition. Pain-related fear and anxiety traits as well as anticipatory fear ratings were positively associated with pain ratings in GPPPD, but not in HC. Further, in HC, a negative association was found between anticipatory fear ratings and brain responses in regions involved in cognitive and affective aspects of pain perception, but not in women with GPPPD. CONCLUSIONS: Women with GPPPD are characterized by increased subjective and brain responses to vestibular pain and, to a lesser extent, its anticipation, with fear and anxiety associated with responses to pain, supporting the introduction of anticipatory fear as a criterion of GPPPD in DSM-5.

Vascular disrupting agent in pancreatic and hepatic tumour allografts: observations of location-dependent efficacy by MRI, microangiography and histomorphology.

BACKGROUND: Tumours growing in organs of different vascular environment could exhibit diverse responses to vascular disrupting agent (VDA). This study was aimed to identify in vivo imaging biomarkers for evaluation of pancreatic and hepatic tumours and comparison of their responses to a VDA Combretastatin A4 Phosphate (CA4P) using multiparametric MRI. METHODS: Male WAG/Rij rats were used for orthotopic pancreatic head tumour and hepatic tumour implantation; tumour growth was monitored by 3D isotropic MRI using a 3.0-T clinic scanner. Therapeutic intervention using CA4P was investigated by in vivo quantitative MRI measurements including T2/T1 relaxation mapping, diffusion kurtosis imaging and dynamic contrast-enhancement (DCE) imaging. Animals were scarified 10 h after CA4P treatment for ex vivo validation using microangiography and histomorphology. RESULTS: State-of-the-art clinical MRI protocols were successfully adapted for imaging small animal tumour with high reliability. One hour after CA4P injection, marked vascular shutdown was detected with DCE MRI in both pancreatic and hepatic tumours. However, 10 h later, therapeutic necrosis was limited in pancreatic tumours compared with that in hepatic tumours (P<0.01). Heterogeneous therapeutic changes were depicted in tumour lesions using pixel-wise Tofts model, which was generated from dynamic T1 mapping. In addition, tumour responses including haemorrhage, oedema and necrosis were detected using quantitative T2/T1 relaxation maps and diffusion kurtosis images, and were validated using histomorphology. CONCLUSIONS: Using multiparametric imaging biomarkers, hepatic tumours were found to be significantly more responsive to CA4P than pancreatic tumours, which could be of reference for designing future clinical trials on this agent.

Characterization of a rat orthotopic pancreatic head tumor model using three-dimensional and quantitative multi-parametric MRI.

The purpose of this study was to investigate the reliability of 3D isotropic MRI and quantitative multi-parametric MRI characterization on an orthotopic pancreatic head tumor model in rats. 3D isotropic T2 -weighted MRI was performed as a routine for tumor longitudinal follow-up and volume estimation. Common bile duct diameter was measured from 3D multiplanar reconstruction. Quantitative multi-parametric measurements including pixel-wise T2 , T1 relaxivity, apparent diffusion coefficient (ADC) and apparent diffusion kurtosis mapping were performed twice throughout tumor growth. Semi-quantitative and quantitative analyses based on an extended Tofts model were applied to region-of-interest-based dynamic contrast-enhanced imaging, followed by contrast ratio measurement on standard contrast-enhanced imaging. Moreover, low-level texture-based analysis was inspected for T2 , T1 , ADC and contrast ratio measurements. Results indicated that multi-parametric MRI showed good reproducibility for tumor characterization; the measurements were not affected by tumor growth. Tumor growth was further confirmed with histology examinations. To conclude, state-of-the-art clinical MRI techniques were translated to this preclinical tumor model with high reliability, and have paved the way for translational oncology studies on this tumor model.

Three-dimensional contrasted visualization of pancreas in rats using clinical MRI and CT scanners.

The purpose of this work was to visualize the pancreas in post-mortem rats with local contrast medium infusion by three-dimensional (3D) magnetic resonance imaging (MRI) and computed tomography (CT) using clinical imagers. A total of 16 Sprague Dawley rats of about 300 g were used for the pancreas visualization. Following the baseline imaging, a mixed contrast medium dye called GadoIodo-EB containing optimized concentrations of Gd-DOTA, iomeprol and Evens blue was infused into the distally obstructed common bile duct (CBD) for post-contrast imaging with 3.0 T MRI and 128-slice CT scanners. Images were post-processed with the MeVisLab software package. MRI findings were co-registered with CT scans and validated with histomorphology, with relative contrast ratios quantified. Without contrast enhancement, the pancreas was indiscernible. After infusion of GadoIodo-EB solution, only the pancreatic region became outstandingly visible, as shown by 3D rendering MRI and CT and proven by colored dissection and histological examinations. The measured volume of the pancreas averaged 1.12 ± 0.04 cm(3) after standardization. Relative contrast ratios were 93.28 ± 34.61% and 26.45 ± 5.29% for MRI and CT respectively. We have developed a multifunctional contrast medium dye to help clearly visualize and delineate rat pancreas in situ using clinical MRI and CT scanners. The topographic landmarks thus created with 3D demonstration may help to provide guidelines for the next in vivo pancreatic MRI research in rodents.

Characterizing the microstructural basis of "unidentified bright objects" in neurofibromatosis type 1: A combined in vivo multicomponent T2 relaxation and multi-shell diffusion MRI analysis.

INTRODUCTION: The histopathological basis of "unidentified bright objects" (UBOs) (hyperintense regions seen on T2-weighted magnetic resonance (MR) brain scans in neurofibromatosis-1 (NF1)) remains unclear. New in vivo MRI-based techniques (multi-exponential T2 relaxation (MET2) and diffusion MR imaging (dMRI)) provide measures relating to microstructural change. We combined these methods and present previously unreported data on in vivo UBO microstructure in NF1. METHODS: 3-Tesla dMRI data were acquired on 17 NF1 patients, covering 30 white matter UBOs. Diffusion tensor, kurtosis and neurite orientation and dispersion density imaging parameters were calculated within UBO sites and in contralateral normal appearing white matter (cNAWM). Analysis of MET2 parameters was performed on 24 UBO-cNAWM pairs. RESULTS: No significant alterations in the myelin water fraction and intra- and extracellular (IE) water fraction were found. Mean T2 time of IE water was significantly higher in UBOs. UBOs furthermore showed increased axial, radial and mean diffusivity, and decreased fractional anisotropy, mean kurtosis and neurite density index compared to cNAWM. Neurite orientation dispersion and isotropic fluid fraction were unaltered. CONCLUSION: Our results suggest that demyelination and axonal degeneration are unlikely to be present in UBOs, which appear to be mainly caused by a shift towards a higher T2-value of the intra- and extracellular water pool. This may arise from altered microstructural compartmentalization, and an increase in 'extracellular-like', intracellular water, possibly due to intramyelinic edema. These findings confirm the added value of combining dMRI and MET2 to characterize the microstructural basis of T2 hyperintensities in vivo.

Longitudinal assessment of chemotherapy-induced alterations in brain activation during multitasking and its relation with cognitive complaints.

PURPOSE: To examine whether cognitive complaints after treatment for breast cancer are associated with detectable changes in brain activity during multitasking. PATIENTS AND METHODS: Eighteen patients who were scheduled to receive chemotherapy performed a functional magnetic resonance imaging multitasking task in the scanner before the start of treatment (t1) and 4 to 6 months after finishing treatment (t2). Sixteen patients who were not scheduled to receive chemotherapy and 17 matched healthy controls performed the same task at matched intervals. Task difficulty level was adjusted individually to match performance across participants. Statistical Parametric Mapping 8 (SPM8) software was used for within-group, between-group, and group-by-time interaction image analyses. RESULTS: Voxel-based paired t tests revealed significantly decreased activation (P < .05) from t1 to t2 at matched performance in the multitasking network of chemotherapy-treated patients, whereas no changes were noted in either of the control groups. At baseline, there were no differences between the groups. Furthermore, in contrast to controls, the chemotherapy-treated patients reported a significant increase in cognitive complaints (P < .05) at t2. Significant (P < .05) correlations were found between these increases and decreases in multitasking-related brain activation. Moreover, a significant group-by-time interaction (P < .05) was found whereby chemotherapy-treated patients showed decreased activation and healthy controls did not. CONCLUSION: These results suggest that changes in brain activity may underlie chemotherapy-induced cognitive complaints. The observed changes might be related to chemotherapy-induced damage to the brain or reduced connectivity between brain regions rather than to changes in effort or changes in functional strategy. To the best of our knowledge, this is the first longitudinal study providing evidence for a relationship between longitudinal changes in cognitive complaints and changes in brain activation after chemotherapy.