Mixed Reality Anatomy Using Microsoft HoloLens and Cadaveric Dissection: A Comparative Effectiveness Study.

PURPOSE: As the amount of curricular material required of medical students increases, less time is available for anatomy; thus, methods to teach anatomy more efficiently and effectively are necessary. In this randomized controlled trial, we looked at the effectiveness of a mixed reality (MR) device to teach musculoskeletal anatomy to medical students compared with traditional cadaveric dissection. METHOD: Participating students were divided into three cohorts. Cohort 1 first studied upper limb anatomy in MR followed by lower limb anatomy through cadaveric dissection. Cohort 2 studied upper limb anatomy with cadaveric dissection followed by lower limb anatomy in MR. After the six sessions, a third cohort of 33 students who never received any teaching in MR was recruited to participate in the final practical exams as a control group. All 64 students completed two practical exams with equivalent content, one in the cadaver lab and one using MR. RESULTS: The average scores were 73.8% + 12.3 on the cadaver exam and 74.2% + 13.0 in MR. There is no statistical difference between these scores (p > 0.05). A correlation was found between the MR practical exam and cadaver practical exam scores (r = 0.74, p < 0.01) across all students. CONCLUSIONS: To our knowledge, this study marks the first time that MR was compared with traditional anatomy learning modalities in a multi-session, group course. Our results clearly indicate that medical students, regardless of the study modality, performed similarly on the MR and the cadaver practical exams.

Delivery of drugs into brain tumors using multicomponent silica nanoparticles.

Glioblastomas are highly lethal cancers defined by resistance to conventional therapies and rapid recurrence. While new brain tumor cell-specific drugs are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. We developed a multicomponent nanoparticle, consisting of an iron oxide core and a mesoporous silica shell that can effectively deliver drugs across the blood-brain barrier into glioma cells. When exposed to alternating low-power radiofrequency (RF) fields, the nanoparticle's mechanical tumbling releases the entrapped drug molecules from the pores of the silica shell. After directing the nanoparticle to target the near-perivascular regions and altered endothelium of the brain tumor via fibronectin-targeting ligands, rapid drug release from the nanoparticles is triggered by RF facilitating wide distribution of drug delivery across the blood-brain tumor interface.

Treatment of glioblastoma using multicomponent silica nanoparticles.

Glioblastomas (GBMs) remain highly lethal. This partially stems from the presence of brain tumor initiating cells (BTICs), a highly plastic cellular subpopulation that is resistant to current therapies. In addition to resistance, the blood-brain barrier limits the penetration of most drugs into GBMs. To effectively deliver a BTIC-specific inhibitor to brain tumors, we developed a multicomponent nanoparticle, termed Fe@MSN, which contains a mesoporous silica shell and an iron oxide core. Fibronectin-targeting ligands directed the nanoparticle to the near-perivascular areas of GBM. After Fe@MSN particles deposited in the tumor, an external low-power radiofrequency (RF) field triggered rapid drug release due to mechanical tumbling of the particle resulting in penetration of high amounts of drug across the blood-brain tumor interface and widespread drug delivery into the GBM. We loaded the nanoparticle with the drug 1400W, which is a potent inhibitor of the inducible nitric oxide synthase (iNOS). It has been shown that iNOS is preferentially expressed in BTICs and is required for their maintenance. Using the 1400W-loaded Fe@MSN and RF-triggered release, in vivo studies indicated that the treatment disrupted the BTIC population in hypoxic niches, suppressed tumor growth and significantly increased survival in BTIC-derived GBM xenografts.

Eddy current-shielded x-space relaxometer for sensitive magnetic nanoparticle characterization.

The development of magnetic particle imaging (MPI) has created a need for optimized magnetic nanoparticles. Magnetic particle relaxometry is an excellent tool for characterizing potential tracers for MPI. In this paper, we describe the design and construction of a high-throughput tabletop relaxometer that is able to make sensitive measurements of MPI tracers without the need for a dedicated shield room.

Parallel transmit excitation at 1.5 T based on the minimization of a driving function for device heating.

PURPOSE: To provide a rapid method to reduce the radiofrequency (RF) E-field coupling and consequent heating in long conductors in an interventional MRI (iMRI) setup. METHODS: A driving function for device heating (W) was defined as the integration of the E-field along the direction of the wire and calculated through a quasistatic approximation. Based on this function, the phases of four independently controlled transmit channels were dynamically changed in a 1.5 T MRI scanner. During the different excitation configurations, the RF induced heating in a nitinol wire immersed in a saline phantom was measured by fiber-optic temperature sensing. Additionally, a minimization of W as a function of phase and amplitude values of the different channels and constrained by the homogeneity of the RF excitation field (B1) over a region of interest was proposed and its results tested on the benchtop. To analyze the validity of the proposed method, using a model of the array and phantom setup tested in the scanner, RF fields and SAR maps were calculated through finite-difference time-domain (FDTD) simulations. In addition to phantom experiments, RF induced heating of an active guidewire inserted in a swine was also evaluated. RESULTS: In the phantom experiment, heating at the tip of the device was reduced by 92% when replacing the body coil by an optimized parallel transmit excitation with same nominal flip angle. In the benchtop, up to 90% heating reduction was measured when implementing the constrained minimization algorithm with the additional degree of freedom given by independent amplitude control. The computation of the optimum phase and amplitude values was executed in just 12 s using a standard CPU. The results of the FDTD simulations showed similar trend of the local SAR at the tip of the wire and measured temperature as well as to a quadratic function of W, confirming the validity of the quasistatic approach for the presented problem at 64 MHz. Imaging and heating reduction of the guidewire were successfully performed in vivo with the proposed hardware and phase control. CONCLUSIONS: Phantom and in vivo data demonstrated that additional degrees of freedom in a parallel transmission system can be used to control RF induced heating in long conductors. A novel constrained optimization approach to reduce device heating was also presented that can be run in just few seconds and therefore could be added to an iMRI protocol to improve RF safety.

Multi-turn transmit coil to increase b1 efficiency in current source amplification.

PURPOSE: A multi-turn transmit surface coil design was presented to improve B1 efficiency when used with current source amplification. METHODS: Three different coil designs driven by an on-coil current-mode class-D amplifier with current envelope feedback were tested on the benchtop and through imaging in a 1.5 T scanner. Case temperature of the power field-effect transistor at the amplifier output stage was measured to evaluate heat dissipation for the different current levels and coil configurations. In addition, a lower power rated device was tested to exploit the potential gain in B1 obtained with the multi-turn coil. RESULTS: As shown both on the benchtop and in a 1.5 T scanner, B1 was increased by almost 3-fold without increasing heat dissipation on the power device at the amplifier's output using a multi-turn surface coil. Similar gain was obtained when connecting a lower power rated field-effect transistor to the multi-turn coil. CONCLUSION: In addition to reduce heat dissipation per B1 in the device, higher B1 per current efficiency allows the use of field-effect transistors with lower current ratings and lower port capacitances, which could improve the overall performance of the on-coil current source transmit system.

Comparison of brain MR images at 1.5T using BLADE and rectilinear techniques for patients who move during data acquisition.

BACKGROUND AND PURPOSE: MR imaging of moving patients can be challenging and motion correction techniques have been proposed though some have associated new artifacts. The objective of this study was to semiquantitatively compare brain MR images of moving patients obtained at 1.5T by using partially radial and rectilinear acquisition techniques. MATERIALS AND METHODS: FLAIR, T2-, T1-, and contrast-enhanced T1-weighted image sets of 25 patients (14-94 years) obtained by using BLADE (like PROPELLER, a partially radial acquisition) and rectilinear techniques in the same imaging session were compared by 2 neuroradiologists in terms of extent of the motion artifact, image quality, and lesion visibility. ICC between opinions of the evaluators was calculated. RESULTS: Of the total of 70 image sets, the motion artifact was small in the partially radial images in 43 and in the rectilinear images in 13, and the opinions of the evaluators were discordant in the remaining 14 sets (ICC = 0.63, P < .05). The quality of partially radial images was higher for 36 sets versus 9 rectilinear sets, with disagreement between the 2 evaluators in the remaining 25 (ICC = 0.15, P < .05). Pathologic lesions were better characterized on 37 sets of partially radial images versus 13 sets of rectilinear images, and opinions of the evaluators differed in 20 sets (ICC = 0.90, P < .05). The neuroradiologists deemed 4 sets of rectilinear images nondiagnostic compared with only 1 set of radial images. CONCLUSIONS: The data demonstrate that our application of BLADE sequences reduces the extent of motion artifacts in brain images of moving patients, improving image quality and lesion characterization.

Control of intravascular catheters using an array of active steering coils.

PURPOSE: To extend the concept of deflecting the tip of a catheter with the magnetic force created in an MRI system through the use of an array of independently controllable steering coils located in the catheter tip, and to present methods for visualization of the catheter and/or surrounding areas while the catheter is deflected. METHODS: An array of steering coils made of 42-gauge wire was built over a 2.5 Fr (0.83 mm) fiber braided microcatheter. Two of the coils were 70 turn axial coils separated by 1 cm, and the third was a 15-turn square side coil that was 2 x 4 mm2. Each coil was driven independently by a pulse width modulation (PWM) current source controlled by a microprocessor that received commands from a MATLAB routine that dynamically set current amplitude and direction for each coil. The catheter was immersed in a water phantom containing 1% Gd-DTPA that was placed at the isocenter of a 1.5 T MRI scanner. Deflections of the catheter tip were measured from image-based data obtained with a real-time radio frequency (RF) spoiled gradient echo sequence (GRE). The small local magnetic fields generated by the steering coils were exploited to generate a hyperintense signal at the catheter tip by using a modified GRE sequence that did not include slice-select rewinding gradients. Imaging and excitation modes were implemented by synchronizing the excitation of the steering coil array with the scanner by ensuring that no current was driven through the coils during the data acquisition window; this allowed visualization of the surrounding tissue while not affecting the desired catheter position. RESULTS: Deflections as large as 2.5 cm were measured when exciting the steering coils sequentially with a 100 mA maximum current per coil. When exciting a single axial coil, the deflection was half this value with 30% higher current. A hyperintense catheter tip useful for catheter tracking was obtained by imaging with the modified GRE sequence. Clear visualization of the areas surrounding the catheter was obtained by using the excitation and imaging mode even with a repetition time (TR) as small as 10 ms. CONCLUSIONS: A new system for catheter steering is presented that allows large deflections through the use of an integrated array of steering coils. Additionally, two imaging techniques for tracking the catheter tip and visualization of surrounding areas, without interference from the active catheter, were shown. Together the demonstrated steerable catheter, control system and the imaging techniques will ultimately contribute to the development of a steerable system for interventional MRI procedures.

CEST-FISP: a novel technique for rapid chemical exchange saturation transfer MRI at 7 T.

Chemical exchange saturation transfer (CEST) and magnetization transfer techniques provide unique and potentially quantitative contrast mechanisms in multiple MRI applications. However, the in vivo implementation of these techniques has been limited by the relatively slow MRI acquisition techniques, especially on high-field MRI scanners. A new, rapid CEST-fast imaging with steady-state free precession technique was developed to provide sensitive CEST contrast in ∼20 sec. In this study at 7 T with in vitro bovine glycogen samples and initial in vivo results in a rat liver, the CEST-fast imaging with steady-state free precession technique was shown to provide equivalent CEST sensitivity in comparison to a conventional CEST-spin echo acquisition with a 50-fold reduction in acquisition time. The sensitivity of the CEST-fast imaging with steady-state free precession technique was also shown to be dependent on k-space encoding with centric k-space encoding providing a 30-40% increase in CEST sensitivity relative to linear encoding for 256 or more k-space lines. Overall, the CEST-fast imaging with steady-state free precession acquisition technique provides a rapid and sensitive imaging platform with the potential to provide quantitative CEST and magnetization transfer imaging data.

A simple geometrical description of the TrueFISP ideal transient and steady-state signal.

An intuitive approach is presented for assessment of the TrueFISP signal behavior in the transient phase and the steady state, based on geometrical considerations in combination with the Bloch equations. Short formulations are derived for the zenith and phase angle determining the direction of the magnetization vector for which a smooth monoexponential decay is obtained even at considerable off-resonance frequencies, thus compactly defining the target of various preparation schemes proposed in literature. A pictorial explanation is provided to illustrate how the interplay between RF excitation and relaxation governs the TrueFISP transient phase and steady state. Closed form expressions are developed that describe the signal evolution, accounting for the influence of T(1), T(2), flip angle, and resonance frequency offset in agreement with recently published studies. These results are obtained directly from basic assumptions, without the need for abstract mathematical treatment or further approximations. The validity of the conceptual framework and the analytical description is verified by simulations based on the Bloch equations as well as with MR phantom experiments. The theory may be used for contrast calculations and has the potential to facilitate improved parameter quantification with magnetization prepared TrueFISP experiments accounting for off-resonance effects.

[Feasibilities and limitations of high field parallel MRI]. / Möglichkeiten und Grenzen der parallelen MRT im Hochfeld.

In medical magnetic resonance imaging (MRI) it is standard to use MR scanners with a field strength of 1.5 Tesla. Recently, an ongoing development to higher field strength can be observed and a new clinical standard at 3.0 Tesla seems to be established. High field MRI with its intrinsic higher signal to noise ratio (SNR) can enable new applications of MRI in medical diagnosis, or can serve to improve existing methods. It is important to note, that the use of high field MRI is not without its limitations. Besides the SNR, other unwanted effects increase with a higher field strength. Without correction, these high field problems cause a serious loss in image quality. An elegant way to address these problems is the use of parallel imaging. In many clinical applications, parallel MRI (pMRI) is part of the standard protocol, because pMRI can enhance virtually every MRI application, without necessarily affecting the contrast behavior of the underlying imaging sequence. In high field MRI, besides the speed advantage of pMRI, the positive influence on high field specific problems and therefore on the image quality will be of major importance.

Resolution enhancement in lung 1H imaging using parallel imaging methods.

Resolution in (1)H lung imaging is limited mainly by the acquisition time. Today, half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences, with short echo time (TE) and short interecho spacing (T(inter)) have found increased use in lung imaging. In this study, a HASTE sequence was used in combination with a partially parallel acquisition (PPA) strategy to increase the spatial resolution in single-shot (1)H lung imaging. To investigate the benefits of using a combination of single-shot sequences and PPA, five healthy volunteers were examined. Compared to conventional imaging methods, substantially increased resolution is obtained using the PPA approach. Representative in vivo (1)H lung images acquired with a HASTE sequence in combination with the generalized autocalibrating partially parallel acquisition (GRAPPA) method, up to an acceleration factor of three, are presented.

VD-AUTO-SMASH imaging.

Recently a self-calibrating SMASH technique, AUTO-SMASH, was described. This technique is based on PPA with RF coil arrays using auto-calibration signals. In AUTO-SMASH, important coil sensitivity information required for successful SMASH reconstruction is obtained during the actual scan using the correlation between undersampled SMASH signal data and additionally sampled calibration signals with appropriate offsets in k-space. However, AUTO-SMASH is susceptible to noise in the acquired data and to imperfect spatial harmonic generation in the underlying coil array. In this work, a new modified type of internal sensitivity calibration, VD-AUTO-SMASH, is proposed. This method uses a VD k-space sampling approach and shows the ability to improve the image quality without significantly increasing the total scan time. This new k-space adapted calibration approach is based on a k-space-dependent density function. In this scheme, fully sampled low-spatial frequency data are acquired up to a given cutoff-spatial frequency. Above this frequency, only sparse SMASH-type sampling is performed. On top of the VD approach, advanced fitting routines, which allow an improved extraction of coil-weighting factors in the presence of noise, are proposed. It is shown in simulations and in vivo cardiac images that the VD approach significantly increases the potential and flexibility of rapid imaging with AUTO-SMASH.

Partially parallel imaging with localized sensitivities (PILS).

In this study a novel partially parallel acquisition method is presented, which can be used to accelerate image acquisition using an RF coil array for spatial encoding. In this technique, Parallel Imaging with Localized Sensitivities (PILS), it is assumed that the individual coils in the array have localized sensitivity patterns, in that their sensitivity is restricted to a finite region of space. Within the PILS model, a detailed, highly accurate RF field map is not needed prior to reconstruction. In PILS, each coil in the array is fully characterized by only two parameters: the center of coil's sensitive region in the FOV and the width of the sensitive region around this center. In this study, it is demonstrated that the incorporation of these coil parameters into a localized Fourier transform allows reconstruction of full FOV images in each of the component coils from data sets acquired with a reduced number of phase encoding steps compared to conventional imaging techniques. After the introduction of the PILS technique, primary focus is given to issues related to the practical implementation of PILS, including coil parameter determination and the SNR and artifact power in the resulting images. Finally, in vivo PILS images are shown which demonstrate the utility of the technique.

SMASH imaging with an eight element multiplexed RF coil array.

SMASH (SiMultaneous Acquisition of Spatial Harmonics) is a technique which can be used to acquire multiple lines of k-space in parallel, by using spatial information from a radiofrequency coil array to perform some of the encoding normally produced by gradients. Using SMASH, imaging speed can be increased up to a maximum acceleration factor equal to the number of coil array elements. This work is a feasibility study which examines the use of SMASH with specialized coil array and data reception hardware to achieve previously unattainable accelerations. An eight element linear SMASH array was designed to operate in conjunction with a time domain multiplexing system to examine the effectiveness of SMASH imaging with as much as eightfold acceleration factors. Time domain multiplexing allowed the multiple independent array elements to be sampled through a standard single-channel receiver. SMASH-reconstructed images using this system were compared with reference images, and signal to noise ratio and reconstruction artifact power were measured as a function of acceleration factor. Results of the imaging experiments showed an almost constant SNR for SMASH acceleration factors of up to eight. Artifact power remained low within this range of acceleration factors. This study demonstrates that efficient SMASH imaging at high acceleration factors is feasible using appropriate hardware, and that time domain multiplexing is a convenient strategy to provide the multiple channels required for rapid imaging with large arrays.

A multicoil array designed for cardiac SMASH imaging.

Recently, several partially parallel acquisition (PPA) techniques have been presented which use spatial information inherent in an RF coil array to reconstruct an image from a reduced set of phase encoding steps. PPAs represent a change in paradigm for the RF coil designer since the focus for arrays to be used with PPAs is to optimize the spatial encoding that is provided by the array. One of the first practical implementations of PPA imaging was demonstrated using the SMASH technique. In this study, we present our results from the construction of the first array designed specifically for cardiac SMASH imaging. Additional design criteria are presented for SMASH arrays that are not considered in conventional array design. Using these design criteria, a four-element array was constructed and then tested in SMASH imaging experiments in the heart. This array has been used in all of our initial cardiac and head SMASH studies with good results.

Dynamic three-dimensional magnetic resonance abdominal angiography and perfusion: implementation and preliminary experience.

Implementation of and preliminary experience with an ultra-fast partial-Fourier radiofrequency (RF) spoiled gradient-echo sequence for gadolinium-enhanced imaging are presented. Three-dimensional angiograms can be acquired in less than 6 seconds. Repetition of the acquisition allows the three-dimensional visualization of several distinct vascular phases. Feasibility is demonstrated in three healthy volunteers. The trade-offs among spatial resolution, temporal resolution, and spatial coverage as well as the technical aspects of gadolinium-enhanced pulse sequences are discussed.

Pulmonary disorders: ventilation-perfusion MR imaging with animal models.

PURPOSE: To demonstrate the capability of magnetic resonance (MR) imaging to assess alteration in regional pulmonary ventilation and perfusion with animal models of airway obstruction and pulmonary embolism. MATERIALS AND METHODS: Airway obstruction was created by inflating a 5-F balloon catheter into a secondary bronchus. Pulmonary emboli were created by injecting thrombi into the inferior vena cava. Regional pulmonary ventilation was assessed with 100% oxygen as a T1 contrast agent. Regional pulmonary perfusion was assessed with a two-dimensional fast low-angle shot, or FLASH, sequence with short repetition and echo times after intravenous administration of gadopentetate dimeglumine. RESULTS: Matched ventilation and perfusion abnormalities were identified in all animals with airway obstruction. MR perfusion defects without ventilation abnormalities were seen in all animals with pulmonary emboli. CONCLUSION: Ventilation and perfusion MR imaging are able to provide regional pulmonary functional information with high spatial and temporal resolution. The ability of MR imaging to assess both the magnitude and regional distribution of pulmonary functional impairment could have an important effect on the evaluation of lung disease.

SMASH imaging.

SMASH imaging is a new MR imaging technique that can be used to multiply the speed of existing imaging sequences. It operates by using an array of radiofrequency (RF) detection coils to perform some of the spatial encoding normally accomplished with magnetic field gradients. The speed of the SMASH technique results from appropriate combinations of coil array RF signals in which multiple lines of image data are gathered simultaneously, rather than one after another. SMASH can be used in conjunction with most rapid imaging sequences, including EPI, resulting in multiplicative gains in imaging speed. This article reviews the basic principles of SMASH imaging, outlines requirements for practical implementation, and presents a variety of in vivo results, highlighting ways in which SMASH may be used to increase imaging speed and to improve image quality for clinical MR imaging applications.

Resolution enhancement in single-shot imaging using simultaneous acquisition of spatial harmonics (SMASH).

Spatial resolution in single-shot imaging is limited by signal attenuation due to relaxation of transverse magnetization. This effect can be reduced by minimizing acquisition times through the use of short interecho spacings. However, the minimum interecho spacing is constrained by limits on gradient switching rates, radiofrequency (RF) power deposition and RF pulse length. Recently, simultaneous acquisition of spatial harmonics (SMASH) has been introduced as a method to acquire magnetic resonance images at increased speeds using a reduced number of phase-encoding gradient steps by extracting spatial information contained in an RF coil array. In this study, it is shown that SMASH can be used to reduce the effects of relaxation, resulting in single-shot images with increased spatial resolution without increasing imaging time. After a brief theoretical discussion, two strategies to reduce signal attenuation and increase spatial resolution in single-shot imaging are introduced and their performance is evaluated in phantom studies. In vivo single-shot echoplanar imaging (EPI), BURST, and half-Fourier single-shot turbo spin-echo (HASTE) images are then presented demonstrating the practical implementation of these resolution enhancement strategies. Images acquired with SMASH show increased spatial resolution and improved image quality when compared with images obtained with the conventional acquisitions. The general principles presented for imaging with SMASH can also be applied to other partially parallel imaging techniques.