Concept for using magnetic particle imaging for intraoperative margin analysis in breast-conserving surgery.

Breast-conserving surgery (BCS) is a commonly utilized treatment for early stage breast cancers but has relatively high reexcision rates due to post-surgical identification of positive margins. A fast, specific, sensitive, easy-to-use tool for assessing margins intraoperatively could reduce the need for additional surgeries, and while many techniques have been explored, the clinical need is still unmet. We assess the potential of Magnetic Particle Imaging (MPI) for intraoperative margin assessment in BCS, using a passively or actively tumor-targeted iron oxide agent and two hardware devices: a hand-held Magnetic Particle detector for identifying residual tumor in the breast, and a small-bore MPI scanner for quickly imaging the tumor distribution in the excised specimen. Here, we present both hardware systems and demonstrate proof-of-concept detection and imaging of clinically relevant phantoms.

Comparison between 8- and 32-channel phased-array receive coils for in vivo hyperpolarized 13 C imaging of the human brain.

PURPOSE: To compare the performance of an 8-channel surface coil/clamshell transmitter and 32-channel head array coil/birdcage transmitter for hyperpolarized 13 C brain metabolic imaging. METHODS: To determine the field homogeneity of the radiofrequency transmitters, B1 + mapping was performed on an ethylene glycol head phantom and evaluated by means of the double angle method. Using a 3D echo-planar imaging sequence, coil sensitivity and noise-only phantom data were acquired with the 8- and 32-channel receiver arrays, and compared against data from the birdcage in transceiver mode. Multislice frequency-specific 13 C dynamic echo-planar imaging was performed on a patient with a brain tumor for each hardware configuration following injection of hyperpolarized [1-13 C]pyruvate. Signal-to-noise ratio (SNR) was evaluated from pre-whitened phantom and temporally summed patient data after coil combination based on optimal weights. RESULTS: The birdcage transmitter produced more uniform B1 + compared with the clamshell: 0.07 versus 0.12 (fractional error). Phantom experiments conducted with matched lateral housing separation demonstrated 8- versus 32-channel mean transceiver-normalized SNR performance: 0.91 versus 0.97 at the head center; 6.67 versus 2.08 on the sides; 0.66 versus 2.73 at the anterior; and 0.67 versus 3.17 on the posterior aspect. While the 8-channel receiver array showed SNR benefits along lateral aspects, the 32-channel array exhibited greater coverage and a more uniform coil-combined profile. Temporally summed, parameter-normalized patient data showed SNRmean,slice ratios (8-channel/32-channel) ranging 0.5-2.00 from apical to central brain. White matter lactate-to-pyruvate ratios were conserved across hardware: 0.45 ± 0.12 (8-channel) versus 0.43 ± 0.14 (32-channel). CONCLUSION: The 8- and 32-channel hardware configurations each have advantages in particular brain anatomy.

The 'virtual DBS population': five realistic computational models of deep brain stimulation patients for electromagnetic MR safety studies.

We design, develop, and disseminate a 'virtual population' of five realistic computational models of deep brain stimulation (DBS) patients for electromagnetic (EM) analysis. We found five DBS patients in our institution' research patient database who received high quality post-DBS surgery computer tomography (CT) examinations of the head and neck. Three patients have a single implanted pulse generator (IPG) and the two others have two IPGs (one for each lead). Moreover, one patient has two abandoned leads on each side of the head. For each patient, we combined the head and neck volumes into a 'virtual CT', from which we extracted the full-length DBS path including the IPG, extension cables, and leads. We corrected topology errors in this path, such as self-intersections, using a previously published optimization procedure. We segmented the virtual CT volume into bones, internal air, and soft tissue classes and created two-manifold, watertight surface meshes of these distributions. In addition, we added a segmented model of the brain (grey matter, white matter, eyes and cerebrospinal fluid) to one of the model (nickname Freddie) that was derived from a T1-weighted MR image obtained prior to the DBS implantation. We simulated the EM fields and specific absorption rate (SAR) induced at 3 Tesla by a quadrature birdcage body coil in each of the five patient models using a co-simulation strategy. We found that inter-subject peak SAR variability across models was independent of the target averaging mass and equal to ~45%. In our simulations of the full brain segmentation and six simplified versions of the Freddie model, the error associated with incorrect dielectric property assignment around the DBS electrodes was greater than the error associated with modeling the whole model as a single tissue class. Our DBS patient models are freely available on our lab website (Webpage of the Martinos Center Phantom Resource 2018 https://phantoms.martinos.org/Main_Page).

Realistic modeling of deep brain stimulation implants for electromagnetic MRI safety studies.

We propose a framework for electromagnetic (EM) simulation of deep brain stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of a DBS patient using post-operative head and neck computed tomography (CT) images stitched together into a 'virtual CT' image covering the entire length of the implant. The body was modeled as homogeneous. The implant path extracted from the CT data contained self-intersections, which we corrected automatically using an optimization procedure. Using the CT-derived DBS path, we built a model of the implant including electrodes, helicoidal internal conductor wires, loops, extension cables, and the implanted pulse generator. We also built four simplified models with straight wires, no extension cables and no loops to assess the impact of these simplifications on safety predictions. We simulated EM fields induced by the RF birdcage body coil in the body model, including at the DBS lead tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the robustness of our simulation results by systematically varying the EM properties of the body model and the position and length of the DBS implant (sensitivity analysis). The topology correction algorithm corrected all self-intersection and curvature violations of the initial path while introducing minimal deformations (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution grid) ranged from 12.8 kW kg-1 (full model, helicoidal conductors) to 43.6 kW kg-1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg-1 (full model, straight conductors) to 73.8 kW kg-1 (no loops, straight conductors) at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak SAR with respect to the conductivity ranged between 18% and 30%. Variability with respect to the position and length of the DBS implant ranged between 9.5% and 27.6%.

Validation of diffusion MRI estimates of compartment size and volume fraction in a biomimetic brain phantom using a human MRI scanner with 300 mT/m maximum gradient strength.

Diffusion microstructural imaging techniques have attracted great interest in the last decade due to their ability to quantify axon diameter and volume fraction in healthy and diseased human white matter. The estimates of compartment size and volume fraction continue to be debated, in part due to the lack of a gold standard for validation and quality control. In this work, we validate diffusion MRI estimates of compartment size and volume fraction using a novel textile axon ("taxon") phantom constructed from hollow polypropylene yarns with distinct intra- and extra-taxonal compartments to mimic white matter in the brain. We acquired a comprehensive set of diffusion MRI measurements in the phantom using multiple gradient directions, diffusion times and gradient strengths on a human MRI scanner equipped with maximum gradient strength (Gmax) of 300 mT/m. We obtained estimates of compartment size and restricted volume fraction through a straightforward extension of the AxCaliber/ActiveAx frameworks that enables estimation of mean compartment size in fiber bundles of arbitrary orientation. The voxel-wise taxon diameter estimates of 12.2 ±â€¯0.9 µm were close to the manufactured inner diameter of 11.8 ±â€¯1.2 µm with Gmax = 300 mT/m. The estimated restricted volume fraction demonstrated an expected decrease along the length of the fiber bundles in accordance with the known construction of the phantom. When Gmax was restricted to 80 mT/m, the taxon diameter was overestimated, and the estimates for taxon diameter and packing density showed greater uncertainty compared to data with Gmax = 300 mT/m. In conclusion, the compartment size and volume fraction estimates resulting from diffusion measurements on a human scanner were validated against ground truth in a phantom mimicking human white matter, providing confidence that this method can yield accurate estimates of parameters in simplified but realistic microstructural environments. Our work also demonstrates the importance of a biologically analogous phantom that can be applied to validate a variety of diffusion microstructural imaging methods in human scanners and be used for standardization of diffusion MRI protocols for neuroimaging research.

Computation of ultimate SAR amplification factors for radiofrequency hyperthermia in non-uniform body models: impact of frequency and tumour location.

PURPOSE: We introduce a method for calculation of the ultimate specific absorption rate (SAR) amplification factors (uSAF) in non-uniform body models. The uSAF is the greatest possible SAF achievable by any hyperthermia (HT) phased array for a given frequency, body model and target heating volume. METHODS: First, we generate a basis-set of solutions to Maxwell's equations inside the body model. We place a large number of electric and magnetic dipoles around the body model and excite them with random amplitudes and phases. We then compute the electric fields created in the body model by these excitations using an ultra-fast volume integral solver called MARIE. We express the field pattern that maximises the SAF in the target tumour as a linear combination of these basis fields and optimise the combination weights so as to maximise SAF (concave problem). We compute the uSAFs in the Duke body models at 10 frequencies in the 20-900 MHz range and for twelve 3 cm-diameter tumours located at various depths in the head and neck. RESULTS: For both shallow and deep tumours, the frequency yielding the greatest uSAF was ∼900 MHz. Since this is the greatest frequency that we simulated, we hypothesise that the globally optimal frequency is actually greater. CONCLUSIONS: The uSAFs computed in this work are very large (40-100 for shallow tumours and 4-17 for deep tumours), indicating that there is a large room for improvement of the current state-of-the-art head and neck HT devices.

Feasibility of using linearly polarized rotating birdcage transmitters and close-fitting receive arrays in MRI to reduce SAR in the vicinity of deep brain simulation implants.

PURPOSE: MRI of patients with deep brain stimulation (DBS) implants is strictly limited due to safety concerns, including high levels of local specific absorption rate (SAR) of radiofrequency (RF) fields near the implant and related RF-induced heating. This study demonstrates the feasibility of using a rotating linearly polarized birdcage transmitter and a 32-channel close-fit receive array to significantly reduce local SAR in MRI of DBS patients. METHODS: Electromagnetic simulations and phantom experiments were performed with generic DBS lead geometries and implantation paths. The technique was based on mechanically rotating a linear birdcage transmitter to align its zero electric-field region with the implant while using a close-fit receive array to significantly increase signal to noise ratio of the images. RESULTS: It was found that the zero electric-field region of the transmitter is thick enough at 1.5 Tesla to encompass DBS lead trajectories with wire segments that were up to 30 degrees out of plane, as well as leads with looped segments. Moreover, SAR reduction was not sensitive to tissue properties, and insertion of a close-fit 32-channel receive array did not degrade the SAR reduction performance. CONCLUSION: The ensemble of rotating linear birdcage and 32-channel close-fit receive array introduces a promising technology for future improvement of imaging in patients with DBS implants. Magn Reson Med 77:1701-1712, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale.

An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond.

Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD).

Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.

Slice accelerated gradient-echo spin-echo dynamic susceptibility contrast imaging with blipped CAIPI for increased slice coverage.

PURPOSE: To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous-multiple-slice (SMS) method. METHODS: Data were acquired on 3 Tesla (T) MR scanners with a 32-channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two-fold slice coverage and same temporal sampling was compared with a standard GESE sequence, both with 2× in-plane acceleration. A signal to noise ratio (SNR) comparison was performed on one healthy subject. Additionally, data with Gadolinium injection were collected on three patients with glioblastoma using both sequences, and perfusion analysis was performed on healthy tissues as well as on tumor. RESULTS: Retained SNR of SMS DSC is 90% for a gradient echo (GE) and 99% for a spin echo (SE) acquisition, compared with a standard acquisition without slice acceleration. Comparing cerebral blood volume maps, it was observed that the results of standard and SMS acquisitions are comparable for both GE and SE images. CONCLUSION: Two-fold slice accelerated DSC MRI achieves similar SNR and perfusion metrics as a standard acquisition, while allowing a significant increase in slice coverage of the brain. The results also point to a possibility to improve temporal sampling rate, while retaining the same slice coverage.

7T MRI of spinal cord injury.

A man with 25 years of mild left neck, arm, and leg paresthesias had initial MRI in 1996 identifying a left C3-4 dorsal horn cavernous hemangioma. In 1997, hemorrhage (C3-7) and resection induced left arm > leg proprioceptive loss and clumsiness. Three months after surgical resection, left upper-body pain recurred; 2 years later, disabling colocalizing itch recurred.(1) In 2012, ultra-high-resolution 7T MRI (figure) localized hemosiderin to specific dorsal horn laminae and detected rostral (C1-3) hypersignal invisible on conventional MRIs, most likely representing Wallerian degeneration.(2) These new imaging findings demonstrate the benefit of high-field spinal cord MRI and generate the hypothesis that his late-onset central itch might be related to delayed white matter degeneration.

Measuring SPIO and Gd contrast agent magnetization using 3 T MRI.

Traditional methods of measuring magnetization in magnetic fluid samples, such as vibrating sample magnetometry (VSM), are typically limited to maximum field strengths of about 1 T. This work demonstrates the ability of MRI to measure the magnetization associated with two commercial MRI contrast agents at 3 T by comparing analytical solutions to experimental imaging results for the field pattern associated with agents in cylindrical vials. The results of the VSM and fitted MRI data match closely. The method represents an improvement over VSM measurements since results are attainable at imaging field strengths. The agents investigated are Feridex, a superparamagnetic iron oxide suspension used primarily for liver imaging, and Magnevist, a paramagnetic, gadolinium-based compound used for tumors, inflammation and vascular lesions. MR imaging of the agents took place in sealed cylindrical vials in the presence of a surrounding volume of deionized water where the effects of the contrast agents had a measurable effect on the water's magnetization in the vicinity of the compartment of contrast agent. A pair of phase images were used to reconstruct a B(0) fieldmap. The resultant B(0) maps in the water region, corrected for shimming and container edge effects, were used to predict the agent's magnetization at 3 T. The results were compared with the results from VSM measurements up to 1.2 T and close correlation was observed. The technique should be of interest to those seeking quantification of the magnetization associated with magnetic suspensions beyond the traditional scope of VSM. The magnetization needs to be sufficiently strong (M(s) >or= 50 Am(2)/kg Fe for Feridex and X(m) >or=5 x 10(-5) m(3)/kg Gd for Magnevist) for a measurable dipole field in the surrounding water. For this reason, the technique is mostly suitable for undiluted agents.

Accelerated radiation damping for increased spin equilibrium (ARISE): a new method for controlling the recovery of longitudinal magnetization.

Control of the longitudinal magnetization in fast gradient-echo (GRE) sequences is an important factor in enabling the high efficiency of balanced steady-state free precession (bSSFP) sequences. We introduce a new method for accelerating the return of the longitudinal magnetization to the +z-axis that is independent of externally applied RF pulses and shows improved off-resonance performance. The accelerated radiation damping for increased spin equilibrium (ARISE) method uses an external feedback circuit to strengthen the radiation damping (RD) field. The enhanced RD field rotates the magnetization back to the +z-axis at a rate faster than T(1) relaxation. The method is characterized in GRE phantom imaging at 3T as a function of feedback gain, phase, and duration, and compared with results from numerical simulations of the Bloch equations incorporating RD. A short period of feedback (10 ms) during a refocused interval of a crushed GRE sequence allowed greater than 99% recovery of the longitudinal magnetization when very little T(2) relaxation had time to occur. An appropriate application might be to improve navigated sequences. Unlike conventional flip-back schemes, the ARISE "flip-back" is generated by the spins themselves, thereby offering a potentially useful building block for enhancing GRE sequences.

Fast slice-selective radio-frequency excitation pulses for mitigating B+1 inhomogeneity in the human brain at 7 Tesla.

A novel radio-frequency (RF) pulse design algorithm is presented that generates fast slice-selective excitation pulses that mitigate B+1 inhomogeneity present in the human brain at high field. The method is provided an estimate of the B+1 field in an axial slice of the brain and then optimizes the placement of sinc-like "spokes" in kz via an L1-norm penalty on candidate (kx, ky) locations; an RF pulse and gradients are then designed based on these weighted points. Mitigation pulses are designed and demonstrated at 7T in a head-shaped water phantom and the brain; in each case, the pulses mitigate a significantly nonuniform transmit profile and produce nearly uniform flip angles across the field of excitation (FOX). The main contribution of this work, the sparsity-enforced spoke placement and pulse design algorithm, is derived for conventional single-channel excitation systems and applied in the brain at 7T, but readily extends to lower field systems, nonbrain applications, and multichannel parallel excitation arrays.