Simultaneous MRI Research Articles

A case of MuSK myasthenia gravis associated with solitary lymphadenopathy and insidious autoimmune‐like diffuse encephalopathy

AbstractWe report an 81‐year‐old woman with anti‐muscle‐specific kinase (MuSK) antibody‐positive myasthenia gravis (MG) associated with solitary lymphadenopathy and insidious encephalopathy. At the age of 74, her myasthenic symptoms were remitted by immunosuppressive therapy and solitary abdominal lymphadenopathy was removed from the mesentery. Histopathological examinations showed follicular hyperplasia with marked IgG4‐positive plasma cell infiltration in the interfollicular connective tissues. Simultaneous head MRI examinations revealed diffuse brain lesions predominantly in the white matter without any neurological symptoms. The biopsied brain specimen showed scattered lymphocyte infiltration around vessels and reactive gliosis without IgG4‐positive plasma cells suggesting an autoimmune‐like encephalopathy. At the age of 81, MuSK‐MG was remittent, but the head MRI abnormalities sustained.

AS1411 aptamer-modified theranostic liposomes co-encapsulating manganese oxide nano-contrast agent and paclitaxel for MRI and therapy of cancer.

With the advantages and development of MRI nano-contrast agents (CAs), increasing number of MRI-based theranostic nanoparticles have emerged. Liposome, as a biosafe nanocarrier has been used phase III trial for cancer treatment. In this study, liposome was employed as a nanocarrier to co-encapsulate MRI nano-contrast agent poly(ethylene glycol)-grafted manganese oxide (PEG-MnO) and anticancer drug paclitaxel (PTX) for the fabrication of a novel theranostic nanocomplex. After being further modified with AS1411 aptamer, the obtained nanoprobe AS1411-liposome-PEG-MnO-PTX displayed the potential of simultaneous MRI diagnosis and therapy of renal carcinoma in vitro and in vivo. It was found that compared with PEG-MnO nano-CA, liposome-PEG-MnO and AS1411-liposome-PEG-MnO presented a stronger MR contrast enhancement effect in the tumor and longer retention time in the tumor region. More importantly, the introduction of AS1411 aptamer further enhanced the MRI effect and the tumor growth inhibition effect, showing its potential use as a theranostic nanoprobe for renal carcinoma.

Functionalization of Gadolinium Chelates Silica Nanoparticle through Silane Chemistry for Simultaneous MRI/64Cu PET Imaging.

Multimodal nanoprobes are highly demanded for biomedical imaging applications to enhance the reliability of the diagnostic results. Among different types of nano-objects, ultrasmall silica gadolinium nanoparticle (SiGdNP) appears as a safe, effective, and versatile platform for this purpose. In this study, a new method to functionalize SiGdNP based on silane chemistry has been reported. Two types of chelating silanes (APTES-DOTAGA and APTES-NODAGA) have been synthesized and grafted on SiGdNP by a simple one-step protocol. This functionalization strategy requires no other reactants or catalyzers and does not compromise the ultrasmall size of the particles. NODAGA-functionalized particle has been labeled with 64Cu isotope and injected intravenously to mice bearing TS/A carcinoma tumor for biodistribution study to demonstrate its potential as a bimodal MRI/PET imaging agent. A fully integrated MRI/PET system was used to simultaneously monitor the distribution of the particle. The results showed that the functionalized particle maintained properties of a renal clearable NP which could rapidly escape through kidneys and had low retention in other organs, especially liver, even though its accumulation in the tumor was modest.

Integrated radio‐frequency/wireless coil design for simultaneous MR image acquisition and wireless communication

An innovative radio-frequency (RF) coil design that allows RF currents both at the Larmor frequency and in a wireless communication band to flow on the same coil is proposed to enable simultaneous MRI signal reception and wireless data transfer, thereby minimizing the number of wired connections in the scanner without requiring any modifications or additional hardware within the scanner bore. As a first application, the proposed integrated RF/wireless coil design was further combined with an integrated RF/shim coil design to perform not only MR image acquisition and wireless data transfer, but also localized B0 shimming with a single coil. Proof-of-concept phantom experiments were conducted with such a coil to demonstrate its ability to simultaneously perform these three functions, while maintaining the RF performance, wireless data integrity, and B0 shimming performance. Performing wirelessly controlled shimming of localized B0 inhomogeneities with the coil substantially reduced the B0 root-mean-square error (>70%) and geometric distortions in echo-planar images without degrading the image quality, signal-to-noise ratio (<1.7%), or wireless data throughput (maximum variance = 0.04Mbps) of the coil. The RF/wireless coil design can provide a solution for wireless data transfer that can be easily integrated into existing MRI scanners for a variety of applications.

Volumetric assessment of spontaneous mechanical activities by simultaneous multi-slice MRI techniques with correlation to muscle fiber orientation.

The purpose of this work was assessment of volumetric characteristics of spontaneous mechanical activities in musculature (SMAMs) by diffusion-weighted simultaneous multi-slice (DW-SMS) imaging and spatial correlation to anatomical structure, as revealed by fusion to fiber tractographic information derived from diffusion-tensor imaging (DTI). The feasibility of using DW-SMS to image spontaneous events in human musculature was assessed by phantom measurements. Series of DW-SMS images and DTI datasets were recorded from the resting calf of three human subjects. Simultaneously recorded SMAMs in multiple slices were analyzed regarding spatial extension by the Kolmogorov-Smirnov test. Direct correlation of spatial distribution of SMAMs and fiber orientation was investigated by mapping of muscle fibers to multi-slice SMAM datasets. The DW-SMS strategy allows simultaneous assessment of SMAMs in several slices of resting skeletal musculature, since 73.9% of SMAM-affected volumes have shown SMAMs in multiple DW-SMS slices. Spatial extension of SMAMs was highly correlated over different simultaneously recorded DW-SMS slices, and affected areas followed the orientation of muscle fibers with a connectivity ratio up to 57.18±14.80% based on event count and connectivity count maps. In 89.2% of all SMAM-affected datasets muscle fiber connectivity was shown in at least two adjacent slices. Direct correlation between SMAMs in human lower leg musculature and underlying anatomical structure was revealed by high muscle fiber connectivity (89.2%). SMAMs have shown a wide distribution along the longitudinal muscle direction (73.9% in multiple DW-SMS slices) with direct involvement of muscle fibers. Correlation between SMAMs in multiple DW-SMS slices and crossing muscular fiber tracts provides evidence that SMAMs result from physiological processes in musculature. Fusion of DW-SMS with DTI facilitates non-invasive studies of muscle fiber involvement in SMAMs in resting muscle.

Functional Connectivity of the Caudate in Schizophrenia Evaluated with Simultaneous Resting-State Functional MRI and Electroencephalography Recordings

Background: Aberrant functional connectivity (FC) is increasingly implicated in the clinical phenomenology of schizophrenia. This study focused on the FC of the cortico-striatal network, which is thought to be disrupted in schizophrenia and to contribute to its clinical manifestations. Methods: We used simultaneous resting-state functional magnetic resonance imaging (rsfMRI) and electroencephalography (EEG) recordings to investigate FC in patients with schizophrenia. The study included 20 patients with schizophrenia and 20 healthy controls (HCs). Simultaneously recorded rsfMRI and EEG data were collected with an MR-compatible amplifier, and rsfMRI data were analyzed with the CONN toolbox to calculate FC. The study focused on the caudate, which was defined as the seed. We also performed between-group comparisons of standardized low-resolution electromagnetic tomography intracortical lagged coherence for each EEG frequency band. Results: Compared to HCs, patients with schizophrenia showed enhanced FC between the caudate nucleus and the posterior cingulate cortex, temporal, and occipital regions on rsfMRI. It is thus possible that HCs have negative FC between these regions, whereas patients with schizophrenia have non-negative FC. The EEG results showed no significant differences in oscillations or in FC between the groups in any frequency band in any region. Conclusions: Increased FC in the caudate may represent aberrant between-network FC resulting from the disruption of segregation between networks.

Simulations of a birdcage coil B1+ field on a human body model for designing a 3T multichannel TMS/MRI head coil array.

This article considers a new type of integrated multichannel Transcranial Magnetic Stimulator and Magnetic Resonance Imaging (TMS/MRI) system at 3T that is currently being designed. The system will enable unprecedented spatiotemporal control of the TMS-induced electric fields (Efields) with simultaneous rapid whole-head MRI acquisition to record the brain activity. A critical design question is how TMS coil elements interact with the transmit field (${\mathrm B}_{1}^{+}$) of the volume coil integrated in 3T MRI systems. In general, the TMS coils are not designed to have any resonant characteristics at the MRI frequency, they may potentially disturb the RF field due to the eddy currents induced. This is especially a concern with a multichannel TMS setup where the subject's head will be largely covered with the stimulation coils. Therefore, we investigated this problem by computational simulations with realistic TMS coil geometries and a birdcage transmit coil in conjunction with a human body model. We compared the ${\mathrm B}_{1}^{+}$ interaction effects of a commercially available MR-compatible TMS coil with our coil prototype. In both cases, the results show small local changes in the transmit field ${\mathrm B}_{1}^{+}$of the birdcage coil. Maximal Average Specific Absorption Rate (SAR) values over 1g tissue were found to be slightly lower when the TMS elements were present. We conclude that it should be feasible and safe to use the conventional body transmit coil even when an array of TMS coils is used.

Optimization of Selective Radio Frequency Pulses for Simultaneous Multi-Slice MRI

Optimization of Selective Radio Frequency Pulses for Simultaneous Multi-Slice MRI

Simulation study of the second-generation MR-compatible SPECT system based on the inverted compound-eye gamma camera design

In this paper, we present simulation studies for the second-generation MRI compatible SPECT system, MRC-SPECT-II, based on an inverted compound eye (ICE) gamma camera concept. The MRC-SPECT-II system consists of a total of 1536 independent micro-pinhole-camera-elements (MCEs) distributed in a ring with an inner diameter of 6 cm. This system provides a FOV of 1 cm diameter and a peak geometrical efficiency of approximately 1.3% (the typical levels of 0.1%–0.01% found in modern pre-clinical SPECT instrumentations), while maintaining a sub-500 μm spatial resolution. Compared to the first-generation MRC-SPECT system (MRC-SPECT-I) (Cai 2014 Nucl. Instrum. Methods Phys. Res. A 734 147–51) developed in our lab, the MRC-SPECT-II system offers a similar resolution with dramatically improved sensitivity and greatly reduced physical dimension. The latter should allow the system to be placed inside most clinical and pre-clinical MRI scanners for high-performance simultaneous MRI and SPECT imaging.

Defining the normal appearance of the temporomandibular joints by magnetic resonance imaging with contrast: a comparative study of children with and without juvenile idiopathic arthritis

BackgroundUp to 80% of children with juvenile idiopathic arthritis (JIA) develop arthritis involving their temporomandibular joint (TMJ). Recent studies have questioned the sensitivity of an abnormal MRI in the diagnosis of active arthritis.Methods122 children without arthritis undergoing contrast MRI of the head were prospectively consented to undergo a simultaneous contrast MRI of their TMJs. As a comparison point, the initial MRI of the TMJ of 35 newly diagnosed children with JIA were retrospectively scored. The presence and size of effusion and contrast enhancement were measured in the left TMJ in all subjects.Results62/122 (51%) controls compared to only 10/35 JIA (29%) patients had an effusion (p = 0.022). Contrast enhancement was present in ≥97% of both groups, although the size of the enhancement was, on average, 0.2 mm larger in controls (1.1 ± 0.24 vs 0.88 ± 0.27 mm, p < 0.001). Among JIA patients, the size of the enhancement correlated inversely with disease duration (r = − 0.475, p = 0.005). Chronic changes were present in none of the controls versus 2/35 (5.5%) of the JIA patients (p = 0.049).ConclusionFindings consistent with minimally active TMJ arthritis appear to be equally likely in children with JIA as compared to non-inflamed controls, while this and other studies confirm that chronic changes are specific to JIA. Thus, small amounts of effusion or contrast enhancement, in the absence of chronic changes, should be interpreted with caution.

Simultaneous PET-MRI Confirms That Cerebral Blood Flow Does Not Confound PET Neuroreceptor Activation Studies.

Positron emission tomography (PET) and endogenous competition paradigms are widely used for studying neuroreceptor activation in humans in vivo. Changes in cerebral blood triggered by the experimentation, such as amphetamine administration, could influence both tracer delivery and washout, thus biasing the results. A recent study tested this assumption in baboons by measuring radiotracer binding with PET while measuring simultaneously cerebral blood flow with arterial spin labeled functional magnetic resonance imaging. Cerebral blood flow was modulated by CO2 inhalation. Hypercapnia led to substantial alterations in blood flow with no detectable alteration in binding of the reversibly binding radiotracers [11C]raclopride and [18F]fallypride. These results rule out a serious confound for the endogenous competition paradigm, and demonstrate the importance of simultaneous PET and MRI measurements when studying brain function.

A Practical Approach to Optimize Scan Protocol for Simultaneous Whole-Body Positron Emission Tomography/Magnetic Resonance Imaging in Cancer Staging.

Objective:The aim of the report is to present time efficient whole-body positron emission tomography/magnetic resonance imaging (PET/MRI) protocol evolved and tested for comprehensive evaluation of cancer patients.Materials and Methods:Whole body as well as regional simultaneous PET and MRI was performed on Biograph mMR (Siemens, Erlangen, Germany) Simultaneous PET/MRI system in 4500 clinical cases of various cancers from 2013 to 2017 with an in-house designed imaging protocol to assess its utility.Results:Using this protocol, the whole body is covered with optimized sequences (T1, T2, short tau inversion recovery, diffusion, and 3D volumetric interpolated breath-held) with PET which has been found adequate for complete metastatic workup in 30–45 min. With region-specific studies, it provides a comprehensive staging workup in an additional 10–15 min. The workflow offered additive advantages of effectively addressing incidentalomas besides being useful in terms of diagnostic utility.Conclusion:The proposed whole-body PET MRI imaging protocol used in a clinical setting is found acceptable and reasonably time efficient to optimally exploit the potentials of the technique in oncology.

Carbon nano-structured neural probes show promise for magnetic resonance imaging applications

Objective. Previous animal studies have demonstrated that carbon nanotube (CNT) electrodes provide several advantages of preferential cell growth and better signal-to-noise ratio (SNR) when interfacing with brain neural tissue. This work explores another advantage of CNT electrodes, namely their MRI compatibility. MRI-compatible neural electrodes that do not produce image artifacts will allow simultaneous co-located functional MRI and neural signal recordings, which will help improve our understanding of the brain. Approach. Prototype CNT electrodes on polyimide substrates are fabricated and tested in vitro and in vivo in rat brain at 9.4 T. To understand the results of the in vitro and in vivo studies, a simulation model based on numerical computation of the magnetic field around a two-dimensional object in a tissue substrate is developed. Main Results. The prototype electrodes are found to introduce negligible image artifacts in structural and functional imaging sequences in vitro and in vivo. Simulation results confirm that CNT prototype electrodes produce less magnetic field distortion than traditional metallic electrodes due to a combination of both superior material properties and geometry. By using CNT films, image artifacts can be nearly eliminated at magnetic fields of strength up to 9.4 T. At the same time, the high surface area of a CNT film provides high charge transfer and enables neural local field potential recordings with an equal or better SNR than traditional electrodes. Significance. CNT film electrodes can be used for simultaneous MRI and electrophysiology in animal models to investigate fundamental neuroscience questions and clinically relevant topics such as epilepsy.

Prospective Evaluation of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging.

68Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (68Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptor (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer (PCa). We present data from the use of 68Ga-RM2 in patients with biochemical recurrence (BCR) of PCa and negative findings on conventional imaging. Methods: We enrolled 32 men with BCR of PCa, who were 59-83 y old (mean ± SD, 68.7 ± 6.4 y). Imaging started at 40-69 min (mean, 50.5 ± 6.8 min) after injection of 133.2-151.7 MBq (mean, 140.6 ± 7.4 MBq) of 68Ga-RM2 using a time-of-flight-enabled simultaneous PET/MRI scanner. T1-weighted, T2-weighted, and diffusion-weighted images were acquired. Results: All patients had a rising level of prostate-specific antigen (PSA) (range, 0.3-119.0 ng/mL; mean, 10.1 ± 21.3 ng/mL) and negative findings on conventional imaging (CT or MRI, and a 99mTc-methylene diphosphonate bone scan) before enrollment. The observed 68Ga-RM2 PET detection rate was 71.8%. 68Ga-RM2 PET identified recurrent PCa in 23 of the 32 participants, whereas the simultaneous MRI scan identified findings compatible with recurrent PCa in 11 of the 32 patients. PSA velocity was 0.32 ± 0.59 ng/mL/y (range, 0.04-1.9 ng/mL/y) in patients with negative PET findings and 2.51 ± 2.16 ng/mL/y (range, 0.13-8.68 ng/mL/y) in patients with positive PET findings (P = 0.006). Conclusion:68Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR of PCa. High uptake in multiple areas compatible with cancer lesions suggests that 68Ga-RM2 is a promising PET radiopharmaceutical for localization of disease in patients with BCR of PCa and negative findings on conventional imaging.

Abstract ID: 223 The promise of the MRI linac: Simultaneous MRI and irradiation

Introduction Image guidance during radiotherapy is widely applied in the current clinic. Prior to treatment a variety of imaging modalities is used to localize and characterize the tumour and the surrounding organs at risk. These data are used to optimize the treatment plan, i.e. optimize the radiation dose delivery. Still, during the course of radiotherapy many sources of geometrical uncertainties exist, leading to treatment margins and with that to unwanted involvement of healthy tissues in the targetted volume. By integrating 1.5 T MRI functionality with a radiotherapy linear accelerator (linac), the anatomy can be visualized during irradiation and thus decreasing the geometrical uncertainties and improve the targetting. Materials and methods Together with Elekta (Stockholm, Sweden) and Philips (Best, The Netherlands) a 1.5 T MRI system is integrated with a 7.2 MV linac. The active shielding of the MRI as well as the layout of the linac is modified to mitigate the magnetic interference. A dedicated cage of Faraday was designed to mitigate the RF interference and a beam window in the MRI was created to allow beam passage. In parallel with the hardware developments a pipeline for daily online and ultimately real-time plan adaptation has been set-up. This enables to adapt the plan as soon as an anatomical change is detected. The pipeline can re-optimize the treatment plan for the latest state of the anatomy while taken into account the dose delivered so far. This loop can be run daily but also on an intra-fraction time scale. A major deviation from conventional systems is that the dose is delivered in the presence of a magnetic field. This affects the dose distribution but also affects dosimeters. The impact of the magnetic field can be investigated and subsequently accounted for by Monte Carlo simulations. By doing so, we can quantify the impact on dose and dosimeters. Results and discussion The first prototype MRI linac gave the proof of concept for simultaneous irradiation and MRI. The second prototype showed MRI guided IMRT. The third prototype in Utrecht is the pre-production MR linac and currently the fourth MR linac is installed, this is the pre-clinical MR linac that will be introduced in the clinic. Currently the system is being accepted and commissioned for clinical introduction. The adaptive treatment pipeline has been shown to converge for regular clinical plans. Also for changing anatomies over the course of days and for changes during a single fraction the dose distribution converges to a clinically acceptable dose distribution. Currently the loop is fast enough, in the order minutes, for daily plan adaptation. We are working on speed optimization for the intra-fraction applications. The impact of the magnetic field has been shown to be an asymmetry in the penumbra, a reduced built updistance and most strikingly a dose increaseat tissue-air interfaces. It was shown that these effects can be mitigated by incorporating the magnetic field effects in the inverse optimization for IMRT. Also the impact on absolute, reference and relative dosimetry has been addressed. All exisiting dosimetry protocols can still be performed, albeit sometimes with adapted procedures and adapted detectors. In summary, the 1.5 T MRI linac is operational in a research setting and work on the clinical introduction is ongoing. The advent of on-line MRI directly from the treatment table enables true on-line adaptive radiotherapy.

Hybrid ultrasound-MR guided HIFU treatment method with 3D motion compensation.

Treatments using high-intensity focused ultrasound (HIFU) in the abdominal region remain challenging as a result of respiratory organ motion. A novel method is described here to achieve 3D motion-compensated ultrasound (US) MR-guided HIFU therapy using simultaneous ultrasound and MRI. A truly hybrid US-MR-guided HIFU method was used to plan and control the treatment. Two-dimensional ultrasound was used in real time to enable tracking of the motion in the coronal plane, whereas an MR pencil-beam navigator was used to detect anterior-posterior motion. Prospective motion compensation of proton resonance frequency shift (PRFS) thermometry and HIFU electronic beam steering were achieved. The 3D prospective motion-corrected PRFS temperature maps showed reduced intrascan ghosting artifacts, a high signal-to-noise ratio, and low geometric distortion. The k-space data yielded a consistent temperature-dependent PRFS effect, matching the gold standard thermometry within approximately 1°C. The maximum in-plane temperature elevation ex vivo was improved by a factor of 2. Baseline thermometry acquired in volunteers indicated reduction of residual motion, together with an accuracy/precision of near-harmonic referenceless PRFS thermometry on the order of 0.5/1.0°C. Hybrid US-MR-guided HIFU ablation with 3D motion compensation was demonstrated ex vivo together with a stable referenceless PRFS thermometry baseline in healthy volunteer liver acquisitions. Magn Reson Med 79:2511-2523, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Radiofrequency applicator concepts for simultaneous MR imaging and hyperthermia treatment of glioblastoma multiforme

Abstract Glioblastoma multiforme is the most frequent and most aggressive malignant brain tumor with de facto no long term curation by the use of current multimodal therapeutic approaches. The efficacy of brachytherapy and enhancing interstitial hyperthermia has been demonstrated. RF heating at ultrahigh fields (B0=7.0T, f=298MHz) has the potential of delivering sufficiently large thermal dosage for hyperthermia of relatively large tumor areas. This work focuses on electromagnetic field (EMF) simulations and provides realistic applicator designs tailored for simultaneous RF heating and MRI. Our simulations took advantage of target volumes derived from patient data, and our preliminary results suggest that RF power can be focused to both a small tumor area and a large clinical target volume.

A novel TOF-PET MRI detector for diagnosis and follow up of the prostate cancer

Prostate cancer is the most common disease in men and the second leading cause of death from cancer. Generic large imaging instruments used in cancer diagnosis have sensitivity, spatial resolution, and contrast which are inadequate for the task of imaging details of a small organ such as the prostate. In addition, multimodality imaging can play a significant role in merging anatomical and functional details coming from simultaneous PET and MRI. Indeed, multiparametric PET/MRI was demonstrated to improve diagnosis, but it suffers from too many false positives. In order to address the above limits of the current techniques, we have proposed, built and tested, thanks to the TOPEM project funded by Italian National Institute of Nuclear Phisics, a prototype of an endorectal PET-TOF/MRI probe. In the applied magnification PET geometry, performance is dominated by a high-resolution detector placed closer to the source. The expected spatial resolution in the selected geometry is about 1.5mm FWHM and efficiency of a factor 2 with respect to what was obtained with the conventional PET scanner. In our experimental studies, we have obtained a timing resolution of ∼ 320 ps FWHM and at the same time a Depth of Interaction (DOI) resolution of under 1mm. Tests also showed that mutual adverse PET-MR effects are minimal. In addition, the matching endorectal RF coil was designed, built and tested. In the next planned studies, we expect that benefiting from the further progress in scintillator crystal surface treatment, in SiPM technology and associated electronics would allow us to significantly improve TOF resolution.

Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study.

Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[18 F]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([18 F]-FMISO). MR-rOEF was determined from separate measurements of T2 , T2 * and relative cerebral blood volume (rCBV) employing a multi-parametric approach for quantification of the blood-oxygenation-level-dependent (BOLD) effect. With respect to [18 F]-FMISO-PET, besides the commonly used late uptake between 120 and 130min ([18 F]-FMISO120-130 min ), we also analyzed the hypoxia specific uptake rate [18 F]-FMISO-k3 , as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [18 F]-FMISO data was sensitive to a low signal-to-noise-ratio, analysis was restricted to high-uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia-related parameter maps revealed that high MR-rOEF values clustered in (edematous) peritumoral tissue, while areas with high [18 F]-FMISO120-130 min concentrated in and around active tumor with disrupted blood-brain barrier, i.e. contrast enhancement in T1 -weighted MRI. Volume-of-interest-based correlations between MR-rOEF and [18 F]-FMISO120-130 min as well as [18 F]-FMISO-k3 , and voxel-wise analyses in individual patients, yielded limited correlations, supporting the notion that [18 F]-FMISO uptake, even after 2h, might still be influenced by perfusion while [18 F]-FMISO-k3 was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR-rOEF, and severe tissue hypoxia, as measured by [18 F]-FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high-grade glioma biology.

Pre-clinical imaging of transgenic mouse models of neuroblastoma using a dedicated 3-element solenoid coil on a clinical 3T platform

Background:The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with clinical studies. Here the utility and sensitivity of anatomical and functional MRI data/biomarkers acquired from transgenic mouse models of neuroblastoma using a dedicated radiofrequency (RF) coil on a clinical 3T scanner was evaluated.Methods:Multiparametric MRI of transgenic mice bearing abdominal neuroblastomas was performed at 3T, and data cross-referenced to that acquired from the same mice on a pre-clinical 7T MRI system. T2-weighted imaging, quantitation of the native longitudinal relaxation time (T1) and the transverse relaxation rate (R2*), and dynamic contrast-enhanced (DCE)-MRI, was used to assess tumour volume, phenotype and response to cyclophosphamide or cabozantinib.Results:Excellent T2-weighted image contrast enabled clear tumour delineation at 3T. Significant correlations of tumour volume (R=0.98, P<0.0001) and R2* (R=0.87, P<0.002) measured at 3 and 7T were established. Mice with neuroblastomas harbouring the anaplastic lymphoma kinase mutation exhibited a significantly slower R2* (P<0.001), consistent with impaired tumour perfusion. DCE-MRI was performed simultaneously on three transgenic mice, yielding estimates of Ktrans for each tumour (median Ktrans values of 0.202, 0.168 and 0.114 min−1). Cyclophosphamide elicited a significant reduction in both tumour burden (P<0.002) and native T1 (P<0.01), whereas cabozantinib induced significant (P<0.01) tumour growth delay.Conclusions:Simultaneous multiparametric MRI of multiple tumour-bearing animals using this coil arrangement at 3T can provide high efficiency/throughput for both phenotypic characterisation and evaluation of novel therapeutics, and facilitate the introduction of functional MRI biomarkers into aligned imaging-embedded clinical trials.