X-ray-Sensitive Doped CaF2-Based MRI Contrast Agents for Local Radiation Dose Measurement.

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.

1H Spin-Lattice Relaxation Processes in Solutions of H2N-Fe3O4 Nanoparticles: Insights from NMR Relaxometry.

1H spin-lattice relaxation experiments have been performed for water and glycerol/water solutions of H2N-Fe3O4 superparamagnetic nanoparticles (NPs) of about 7 nm diameter. The experiments encompass a broad frequency range covering 3 orders of magnitude, from 10 kHz to 10 MHz (referring to 1H resonance frequency), and have been performed in the temperature range from 298 to 313 K, varying the concentration of the superparamagnetic species. This extensive dataset has been used for twofold purposes. The first one is to serve as a challenge for thorough tests of theoretical models describing nuclear relaxation in solutions of superparamagnetic NPs, depending on their magnetic properties and dynamics of the solvent molecules. The challenge is posed by the wish to reproduce the data in a broad range of magnetic fields (not only at high fields) and by the need to explain the differences in the relaxation scenarios for water and glycerol/water solutions by varying only the solvent parameters. The second purpose is to get insights into the magnetic properties (electronic relaxation properties) of the nanoparticles due to their high applicational potential.

Fe3O4 Magnetic Nanoparticles Obtained by the Novel Aerosol-Based Technique for Theranostic Applications.

This work is aimed at presenting a novel aerosol-based technique for the synthesis of magnetite nanoparticles (Fe3O4 NPs) and to assess the potential medical application of their dispersions after being coated with TEA-oleate. Refinement of the processing conditions led to the formation of monodispersed NPs with average sizes of ∼5-6 nm and narrow size distribution (FWHM of ∼3 nm). The NPs were coated with Triethanolammonium oleate (TEA-oleate) to stabilize them in water dispersion. This allowed obtaining the dispersion, which does not sediment for months, although TEM and DLS studies have shown the formation of small agglomerates of NPs. The different behaviors of cancer and normal cell lines in contact with NPs indicated the diverse mechanisms of their interactions with Fe3O4 NPs. Furthermore, the studies allowed assessment of the prospective theranostic application of magnetite NPs obtained using the aerosol-based technique, particularly magnetic hyperthermia and magnetic resonance imaging (MRI).

Contrast Enhancement in MRI Using Combined Double Action Contrast Agents and Image Post-Processing in the Breast Cancer Model.

Gd- and Fe-based contrast agents reduce T1 and T2 relaxation times, respectively, are frequently used in MRI, providing improved cancer detection. Recently, contrast agents changing both T1/T2 times, based on core/shell nanoparticles, have been introduced. Although advantages of the T1/T2 agents were shown, MR image contrast of cancerous versus normal adjacent tissue induced by these agents has not yet been analyzed in detail as authors considered changes in cancer MR signal or signal-to-noise ratio after contrast injection rather than changes in signal differences between cancer and normal adjacent tissue. Furthermore, the potential advantages of T1/T2 contrast agents using image manipulation such as subtraction or addition have not been yet discussed in detail. Therefore, we performed theoretical calculations of MR signal in a tumor model using T1-weighted, T2-weighted, and combined images for T1-, T2-, and T1/T2-targeted contrast agents. The results from the tumor model are followed by in vivo experiments using core/shell NaDyF4/NaGdF4 nanoparticles as T1/T2 non-targeted contrast agent in the animal model of triple negative breast cancer. The results show that subtraction of T2-weighted from T1-weighted MR images provides additional increase in the tumor contrast: over two-fold in the tumor model and 12% in the in vivo experiment.

A truncated twisted solenoid RF phase gradient transmit coil for TRASE MRI.

Transmit array spatial encoding (TRASE) is an MR imaging technique that achieves k-space encoding through the use of phase gradients in the RF transmit field. Without requiring B0 gradient fields, TRASE MRI can be performed using significantly cheaper bi-planar permanent magnets or Halbach arrays. For TRASE encoding with these magnets, the twisted solenoid has been demonstrated as the most efficient RF transmit coil; however, this specific geometry results in a long coil with a relatively short imaging volume. We introduce a new truncated design to increase the usable imaging volume relative to the coil length. Based on simulations of optimal parameters, a 200 mm long, 100 mm inner diameter coil pair was constructed with an imaging volume 100 mm in length and 80 mm in diameter. The coil pair was tested using an un-shimmed 2.84 MHz Halbach array. Results indicate the truncated design can create a similar imaging volume and quality to the untruncated version whilst significantly reducing the length of the coil by as much as a half.

Target-Specific Magnetic Resonance Imaging of Human Prostate Adenocarcinoma Using NaDyF4-NaGdF4 Core-Shell Nanoparticles.

We illustrate the development of NaDyF4-NaGdF4 core-shell nanoparticles (NPs) for targeting prostate cancer cells using a preclinical 9.4 T magnetic resonance imaging (MRI) of live animals. The NPs composed of paramagnetic Dy3+ and Gd3+ (T2- and T1-contrast agents, respectively) demonstrate proton relaxivities of r1 = 20.2 mM-1 s-1 and r2 = 32.3 mM-1 s-1 at clinical 3 T and r1 = 9.4 mM-1 s-1 and r2 = 144.7 mM-1 s-1 at preclinical 9.4 T. The corresponding relaxivity values per NP are r1 = 19.4 × 105 mMNP-1 s-1 and r2 = 33.0 × 105 mMNP-1 s-1 at 3 T and r1 = 9.0 × 105 mMNP-1 s-1 and r2 = 147.0 × 105 mMNP-1 s-1 at 9.4 T. In vivo active targeting of human prostate tumors grown in nude mice revealed docking of anti-prostate-specific membrane antigen (PSMA) antibody-tagged NPs at tumor sites post-24 h of their intravenous injection. On the other hand, in vivo passive targeting showed preferential accumulation of NPs at tumor sites only within 2 h of their injection, ascribed to the enhanced permeation and retention effect of the tumor. A biodistribution study employing the harvested organs of mice, post-24 h injection of NPs, quantified active targeting as nearly twice as efficient as passive targeting. These outcomes provide potential opportunities for noninvasive diagnosis using NaDyF4-NaGdF4 core-shell NPs for target-specific MRI.

Simple compensation method for improved half-pulse excitation profile with rephasing gradient.

PURPOSE: To improve the slice profile quality obtained by RF half-pulse excitation for 2D-UTE applications. METHODS: The overall first-order and zero-order phase errors along the slice-selection direction were obtained with the help of an optimization task to minimize the out-of-slice signal contamination from the calibration 1-dimenisonal (1D) profile data. The time-phase-error evolution was approximated from the k-space readout data, which were acquired primarily for correction of the readout trajectories during data regridding to the rectilinear grids. The correction of the slice profile was achieved by rephasing gradient pulses applied immediately after the end of excitation. The total prescan calibration typically took less than 2 minutes. RESULTS: The improved image quality using the proposed calibration method was demonstrated both on phantoms and on ankle images obtained from healthy volunteers. It was demonstrated that calibration can be performed either as a separate water phantom measurement or directly as a prescan procedure. CONCLUSION: The slice-profile distortion from the half-pulse excitation could substantially affect the overall fidelity of 2D-UTE images. The presented experiments proved that the image quality could be substantially increased by application of the proposed slice-correction method.

A high duty-cycle, multi-channel, power amplifier for high-resolution radiofrequency encoded magnetic resonance imaging.

OBJECTIVE: A radiofrequency (RF) power amplifier is an essential component of any magnetic resonance imaging (MRI) system. Unfortunately, no commercial amplifier exists to fulfill the needs of the transmit array spatial encoding (TRASE) MRI technique, requiring high duty cycle, high RF output power and independently controlled multi-channel capability. Thus, an RF amplifier for TRASE MRI is needed. MATERIALS AND METHODS: A dual-channel RF power amplifier dedicated for TRASE at 0.22 T (9.27 MHz) was designed and constructed using commercially available components. The amplifier was tested on the bench and used a 0.22 T MRI system with a twisted solenoid and saddle RF coil combination capable of a single-axis TRASE. RESULTS: The amplifier is capable of sequential, dual-channel operation up to 50% duty cycle, 1 kW peak output and highly stable 100 µs RF pulse trains. High spatial resolution one-dimensional TRASE was obtained with the power amplifier to demonstrate its capability. CONCLUSION: The constructed amplifier is the first prototype that meets the requirements of TRASE rectifying limitations of duty cycle and timing presented by commercial RF amplifiers. The amplifier makes possible future high resolution in vivo TRASE MRI.

Bifunctional Pyrrolidin-2-one Terminated Manganese Oxide Nanoparticles for Combined Magnetic Resonance and Fluorescence Imaging.

Multimodal probes are an asset for simplified, improved medical imaging. In particular, fluorescence and magnetic resonance imaging (MRI) are sought-after combined capabilities. Here, we show that pyrrolidin-2-one-capped manganese oxide nanoparticles (MnOpyrr NPs) combine MRI with fluorescence microscopy to function as efficient bifunctional bio-nanoprobes. We employ a one-pot synthesis for ca. 10 nm MnO NPs, wherein manganese(II) 2,4-pentadionate is thermally decomposed using pyrrolidin-2-one as a solvent and capping ligand. The MnOpyrr NPs are soluble in water without any further postsynthetic modifications. The r1 relaxivity and r2 /r1 ratio indicate that these NPs are potential T1 MRI contrast agents at clinical (3 T) and ultrahigh (9.4 T) magnetic fields. Serendipitously, the as-prepared NPs are photoluminescent. The unexpected luminescence is ascribed to the modification of the pyrrolidin-2-one during the thermal treatment. MnOpyrr NPs are successfully used to enable fluorescence microscopy of HeLa cells, demonstrating bifunctional imaging capabilities. A low cytotoxic response in two distinct cell types (HeLa, HepG2) supports the suitability of MnOpyrr NPs for biological imaging applications.

Challenges in developing a magnetic resonance-compatible haptic hand-controller for neurosurgical training.

A haptic device is an actuated human-machine interface utilized by an operator to dynamically interact with a remote environment. This interaction could be virtual (virtual reality) or physical such as using a robotic arm. To date, different mechanisms have been considered to actuate the haptic device to reflect force feedback from the remote environment. In a low-force environment or limited working envelope, the control of some actuation mechanisms such as hydraulic and pneumatic may be problematic. In the development of a haptic device, challenges include limited space, high accuracy or resolution, limitations in kinematic and dynamic solutions, points of singularity, dexterity as well as control system development/design. Furthermore, the haptic interface designed to operate in a magnetic resonance imaging environment adds additional challenges related to electromagnetic interference, static/variable magnetic fields, and the use of magnetic resonance-compatible materials. Such a device would allow functional magnetic resonance imaging to obtain information on the subject's brain activity while performing a task. When used for surgical trainees, functional magnetic resonance imaging could provide an assessment of surgical skills. In this application, the trainee, located supine within the magnet bore while observing the task environment on a graphical user interface, uses a low-force magnetic resonance-compatible haptic device to perform virtual surgical tasks in a limited space. In the quest to develop such a device, this review reports the multiple challenges faced and their potential solutions. The review also investigates efforts toward prototyping such devices and classifies the main components of a magnetic resonance-compatible device including actuation and sensory systems and materials used.

Influence of k-space trajectory corrections on proton density mapping with ultrashort echo time imaging: Application for imaging of short T2 components in white matter.

PURPOSE: To evaluate the impact of MR gradient system imperfections and limitations for the quantitative mapping of short T2* signals performed by ultrashort echo time (UTE) acquisition approach. MATERIALS AND METHODS: The measurement of short T2* signals from a phantom and a healthy volunteer study (8 subjects of average age 28 ±â€¯4 years) were performed on a 3T scanner. The characteristics of the gradient system were obtained using calibration method performed directly on the measured subject or phantom. This information was used to calculate the actual sampling trajectory with the help of a parametric eddy current model. The actual sample positions were used to reconstruct corrected images and compared with uncorrected data. RESULTS: Comparison of both approaches, i.e., without and with correction of k-space sampling trajectories revealed substantial improvement when correction was applied. The phantom experiments demonstrate substantial in-plane signal intensity variations for uncorrected sampling trajectories. In the case of the volunteer study, this led to significant differences in relative proton density (RPD) estimation between the uncorrected and corrected data (P = 0.0117 by Wilcoxon matched-pairs test) and provides for about ~15% higher values for short T2* components of white matter (WM) in the case of uncorrected images. CONCLUSION: The imperfection of the applied gradients could induce errors in k-space data sampling which further propagates into the fidelity of the UTE images and jeopardizes precision of quantification. However, the study proved that measurement of gradient errors together with correction of sample positions can contribute to increased accuracy and unbiased characterization of short T2* signals.

Correction to: LyP-1 Conjugated Nanoparticles for Magnetic Resonance Imaging of Triple Negative Breast Cancer.

This article was updated to correct the spelling of B. Gino Fallone's name; it is correct as displayed above. Correction to: Mol Imaging Biol (2017). DOI: https://doi.org/10.1007/s11307-017-1140-4.

LyP-1 Conjugated Nanoparticles for Magnetic Resonance Imaging of Triple Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, or Her2/neu. Both diagnosis and treatment of TNBC remain a clinical challenge. LyP-1 is a cyclic 9 amino acid peptide that can bind to breast cancer cells. The goal of this study was to design and characterize LyP-1 conjugated to fluorescent iron oxide nanoparticles (LyP-1-Fe3O4-Cy5.5) as a contrast agent for improved and specific magnetic resonance imaging (MRI) in a preclinical model of TNBC. PROCEDURES: The binding of LyP-1-Fe3O4-Cy5.5 to MDA-MB-231 TNBC cells was evaluated and compared to scrambled peptide bio-conjugated to iron oxide nanoparticles (Ctlpep-Fe3O4-Cy5.5) as a negative control. Following the in vitro study, the MDA-MB-231 cells were injected into mammary glands of nude mice. Mice were divided into two groups: control group received Ctlpep- Fe3O4-Cy5.5 and LyP-1 group received LyP-1-Fe3O4-Cy5.5 (tail vein injection at 2 mg/kg of Fe3O4). Mice were imaged with an in vivo fluorescence imager and a 9.4 T MRI system at various time points after contrast agent injection. The T2 relaxation time was measured to observe accumulation of the contrast agent in breast tumor and muscle for both targeted and non-targeted contrast agents. RESULTS: Immunofluorescence revealed dense binding of the LyP-1-Fe3O4-Cy5.5 contrast agent to MDA-MB-231 cells; while little appreciable binding was observed to the scrambled negative control (Ctlpep-Fe3O4-Cy5.5). Optical imaging performed in tumor-bearing mice showed increased fluorescent signal in mammary gland of animals injected by LyP-1-Fe3O4-Cy5.5 but not Ctlpep- Fe3O4-Cy5.5. The results were confirmed ex vivo by the 2.6-fold increase of fluorescent signal from LyP-1-Fe3O4-Cy5.5 in extracted tumors when compared to the negative control. In MR imaging studies, there was a statistically significant (P < 0.01) difference in normalized T2 between healthy breast and tumor tissue at 1, 2, and 24 h post injection of the LyP-1-Fe3O4-Cy5.5. In animals injected with LyP-1-Fe3O4, distinct ring-like structures were observed with clear contrast between the tumor core and rim. CONCLUSION: The results demonstrate that LyP-1-Fe3O4 significantly improves MRI contrast of TNBC, hence has the potential to be exploited for the specific delivery of cancer therapeutics.

K-space trajectory mapping and its application for ultrashort Echo time imaging.

MR images are affected by system delays and gradient field imperfections which induce discrepancies between prescribed and actual k-space trajectories. This could be even more critical for non-Cartesian data acquisitions where even a small deviation from the assumed k-space trajectory results in severe image degradation and artifacts. Knowledge of the actual k-space trajectories is therefore crucial and can be incorporated in the reconstruction of high quality non-Cartesian images. A novel MR method for the calibration of actual gradient waveforms was developed using a combination of phase encoding increments and subsequent detection of the exact time point at which the corresponding trajectory is crossing the k-space origin. The measured sets of points were fitted to a parametrical model to calculate the complete actual acquisition trajectory. Measurements performed on phantoms and volunteers, positioned both in- and off-isocenter of the magnet, clearly demonstrate the improvement in reconstructed ultrashort echo time (UTE) images, when information from calibration of k-space sampling trajectories is employed in the MR image reconstruction procedure. The unique feature of the proposed method is its robustness and simple experimental setup, making it suitable for quick acquisition trajectory calibration procedures e.g. for non-Cartesian radial fast imaging.

Site-specific conjugation of the quencher on peptide's N-terminal for the synthesis of a targeted non-spreading activatable optical probe.

Optical imaging offers high sensitivity and portability at low cost. The design of 'smart' or 'activatable' probes can decrease the background noise and increase the specificity of the signal. By conjugating a fluorescent dye and a compatible quencher on each side of an enzyme's substrate, the signal remains in its 'off ' state until it reaches the area where a specific enzyme is expressed. However, the signal can leak from that area unless the dye is attached to a molecule able to bind to a specific target also presented in that area. The aim of this study was to (i) specifically conjugate the quencher on the α-amino group of the peptide's N-terminus, (ii) conjugate the dye on the ε-amino group of a lysine in C-terminus, and (iii) conjugate the carboxyl group of the peptide's C-terminus to an amino group present on an antibody, using carbodiimide chemistry. The use of protecting groups, such as Boc or Fmoc, to allow site-specific conjugation, presents several drawbacks including 'on beads labeling', additional steps required for deprotection and removal from the resin, decreased yield, and dye degradation. A method of preferential labeling of α-amino N-terminal group in slightly acidic solution, proposed by Selo et al. (1996) has partially solved the problem. The present study reports improvements of the method allowing to (i) avoid the homo-bilabeling, (ii) increase the yield of the N-terminal labeling by two folds, and (iii) decrease the cost by 44-fold. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis.

OBJECTIVE: To assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL). MATERIALS AND METHODS: BALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASHTM and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging. RESULTS: The average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min-1 (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining. CONCLUSIONS: Both the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

Evaluation of blood-brain barrier-stealth nanocomposites for in situ glioblastoma theranostics applications.

The blood-brain barrier (BBB) is a physiological structure of the blood vessels in the brain. The BBB efficiently traps most therapeutic drugs in the blood vessels and stops them from entering the brain tissue, resulting in a decreased therapeutic efficiency. In this study, we developed BBB-stealth nanocomposites composed of iron oxide (Fe3O4) nanoparticles (NPs) as a safe nanocarrier for glioblastoma therapy. We showed the antitumor activity of Dox/alg-Fe3O4 NPs using in vitro and in vivo tests. We demonstrated that G23-alg-Fe3O4 NPs crossed the BBB and entered the brain. In situ glioblastoma tumor-bearing mice were used to successfully evaluate the antitumor activity of G23-Dox/alg-Fe3O4 NPs. Magnetic resonance imaging (MRI) and bioluminescence imaging (BLI) confirmed the BBB crossing. The BBB-stealth nanocomposites show great potential for a proof-of-concept clinical trial as a theranostics platform for human brain tumor therapy.

HyperCEST detection of cucurbit[6]uril in whole blood using an ultrashort saturation Pre-pulse train.

Xenon based biosensors have the potential to detect and localize biomarkers associated with a wide variety of diseases. The development and nuclear magnetic resonance (NMR) characterization of cage molecules which encapsulate hyperpolarized xenon is imperative for the development of these xenon biosensors. We acquired (129) Xe NMR spectra, and magnetic resonance images and a HyperCEST saturation map of cucurbit[6]uril (CB6) in whole bovine blood. We observed a mean HyperCEST depletion of 84% (n = 5) at a concentration of 5 mM and 74% at 2.5 mM. Additionally, we collected these data using a pulsed HyperCEST saturation pre-pulse train with a SAR of 0.025 W/kg which will minimize any potential RF heating in animal or human tissue. Copyright © 2016 John Wiley & Sons, Ltd.

Hyperpolarized and inert gas MRI: the future.

Magnetic resonance imaging (MRI) is a potentially ideal imaging modality for noninvasive, nonionizing, and longitudinal assessment of disease. Hyperpolarized (HP) agents have been developed in the past 20 years for MR imaging, and they have the potential to vastly improve MRI sensitivity for the diagnosis and management of various diseases. The polarization of nuclear magnetic resonance (NMR)-sensitive nuclei other than (1)H (e.g., (3)He, (129)Xe) can be enhanced by a factor of up to 100,000 times above thermal equilibrium levels, which enables direct detection of the HP agent with no background signal. In this review, a number of HP media applications in MR imaging are discussed, including HP (3)He and (129)Xe lung imaging, HP (129)Xe brain imaging, and HP (129)Xe biosensors. Inert fluorinated gas MRI, which is a new lung imaging technique that does not require hyperpolarization, is also briefly discussed. This technique will likely be an important future direction for the HP gas lung imaging community.

Symmetry of the fornix using diffusion tensor imaging.

PURPOSE: To: 1) Present fornix tractography in its entirety for 20 healthy individuals to assess variability. 2) Provide individual and groupwise whole tract diffusion parameter symmetry assessments prior to clinical application. 3) Compare whole tract diffusion parameter assessments with tract-based spatial statistics (TBSS). MATERIALS AND METHODS: Diffusion tensor imaging (DTI) data were acquired on a 3T Siemens magnetic resonance imaging (MRI) system using a single-shot spin echo planar imaging (EPI) sequence. Individual fornix tractography was conducted and whole tract diffusion parameter symmetries assessed. Whole tract results were compared with asymmetry contrasts conducted with voxelwise statistical analysis of diffusion parameters using TBSS. RESULTS: The fornix tract could be visualized in its entirety including the columns, body, crura, and fimbria. Contrary to the crus and body, there were some tractography inconsistencies of the columns and fimbria across subjects. Although whole tract diffusion parameter asymmetries were nonsignificant, fractional anisotropy (FA) values bordered on statistical significance (P = 0.052). Using TBSS, significant FA asymmetries were identified (P ≤ 0.01, corrected). CONCLUSION: The findings demonstrate consistency of fornix tractography as well as some variability in the columns and fimbria. While parametric assessment demonstrates diffusion parameter symmetry, permutation-based TBSS analysis reveals significant FA asymmetries in the crura and fimbriae.