Functional magnetic particle imaging (fMPI) of cerebrovascular changes in the rat brain during hypercapnia.

Objective.Non-invasive functional brain imaging modalities are limited in number, each with its own complex trade-offs between sensitivity, spatial and temporal resolution, and the directness with which the measured signals reflect neuronal activation. Magnetic particle imaging (MPI) directly maps the cerebral blood volume (CBV), and its high sensitivity derives from the nonlinear magnetization of the superparamagnetic iron oxide nanoparticle (SPION) tracer confined to the blood pool. Our work evaluates functional MPI (fMPI) as a new hemodynamic functional imaging modality by mapping the CBV response in a rodent model where CBV is modulated by hypercapnic breathing manipulation.Approach.The rodent fMPI time-series data were acquired with a mechanically rotating field-free line MPI scanner capable of 5 s temporal resolution and 3 mm spatial resolution. The rat's CBV was modulated for 30 min with alternating 5 min hyper-/hypocapnic states, and processed using conventional fMRI tools. We compare our results to fMRI responses undergoing similar hypercapnia protocols found in the literature, and reinforce this comparison in a study of one rat with 9.4T BOLD fMRI using the identical protocol.Main results.The initial image in the time-series showed mean resting brain voxel SNR values, averaged across rats, of 99.9 following the first 10 mg kg-1SPION injection and 134 following the second. The time-series fit a conventional General Linear Model with a 15%-40% CBV change and a peak pixel CNR between 12 and 29, 2-6× higher than found in fMRI.Significance.This work introduces a functional modality with high sensitivity, although currently limited spatial and temporal resolution. With future clinical-scale development, a large increase in sensitivity could supplement other modalities and help transition functional brain imaging from a neuroscience tool focusing on population averages to a clinically relevant modality capable of detecting differences in individual patients.

Optimization of MRI Gradient Coils With Explicit Peripheral Nerve Stimulation Constraints.

Peripheral Nerve Stimulation (PNS) limits the acquisition rate of Magnetic Resonance Imaging data for fast sequences employing powerful gradient systems. The PNS characteristics are currently assessed after the coil design phase in experimental stimulation studies using constructed coil prototypes. This makes it difficult to find design modifications that can reduce PNS. Here, we demonstrate a direct approach for incorporation of PNS effects into the coil optimization process. Knowledge about the interactions between the applied magnetic fields and peripheral nerves allows the optimizer to identify coil solutions that minimize PNS while satisfying the traditional engineering constraints. We compare the simulated thresholds of PNS-optimized body and head gradients to conventional designs, and find an up to 2-fold reduction in PNS propensity with moderate penalties in coil inductance and field linearity, potentially doubling the image encoding performance that can be safely used in humans. The same framework may be useful in designing and operating magneto- and electro-stimulation devices.

Optimizing selective stimulation of peripheral nerves with arrays of coils or surface electrodes using a linear peripheral nerve stimulation metric.

OBJECTIVE: We present a PNS oracle, which solves these computation time and linearity problems and is, therefore, well-suited for fast optimization of voltage distributions in contact electrode arrays and current drive patterns in non-contact magnetic coil arrays. APPROACH: The PNS oracle metric for a nerve fiber is computed from an electric field map using only linear operations (projection, differentiation, convolution, scaling). Due to its linearity, this PNS metric can be precomputed for a set of coil or electrode segments, allowing rapid PNS prediction and comparison of any possible coil or electrode stimulation configuration constructed from this set. The PNS oracle is closely related to the classical activating function and modified driving functions but is adjusted to better correlate with full neurodynamic modeling of myelinated mammalian nerves. MAIN RESULTS: We validated the PNS oracle in three MRI gradient coils and two body models and found good correlation between the PNS oracle and the full neurodynamic modeling approach (R 2 > 0.995). Finally, we demonstrated its potential utility by optimizing the driving currents and voltages of arrays of 108 magnetic coils or 108 contact electrodes to selectively stimulate target nerves in the lower leg. SIGNIFICANCE: Peripheral nerve stimulation (PNS) by electromagnetic fields can be accurately simulated using coupled electromagnetic and neurodynamic modeling. Such simulations are slow and non-linear in the electric field, which makes it difficult to iteratively optimize coil and electrode configurations or drive patterns aiming to avoid PNS or to initiate it for therapeutic purposes.

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.

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.

In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing.

The magnetic resonance imaging (MRI)-detectable T1 contrast agent manganese (Mn2+) has recently been introduced as a neural tracer in rodents, birds, and monkeys. We have tested to what extent this in vivo method is useful for three-dimensional (3-D) survey of connectivity patterns in the rat somatosensory system. A commonly available 3 T human clinical MRI scanner was used to trace neural pathways following focal injection of manganese chloride (MnCl2) in the somatosensory cortex. Six to 10 h after MnCl2 injection, we found significant signal enhancement in major projection systems, including corticocortical, corticostriatal, corticothalamic, corticotectal, corticopontine, and corticospinal pathways. To facilitate the assignment of anatomic localization to the observed Mn2+ signal enhancement, we registered the MRI data with a 3-D digital reconstruction of a stereotaxic rat brain atlas. Across-animal comparison using the digital model allowed demonstration of a corticothalamic 3-D topographic organization in agreement with previously published two-dimensional topographic schemes based on classical neural tracing data. We conclude that anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization across multiple brain regions. The method allows a higher data throughput for 3-D studies of large-scale brain connectivity than conventional methods based on tissue sectioning.