Improving magnetic resonance spectroscopy in the brainstem periaqueductal gray using spectral registration

Purpose: Functional understanding of the periaqueductal gray (PAG), a clinically relevant brainstem region, can be advanced using ¹H‐MRS. However, the PAG's small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve ¹H‐MRS quality in the PAG using spectral registration for frequency and phase error correction; (2) investigate whether spectral registration is particularly useful in cases of greater head motion; and (3) examine metabolite quantification using literature‐based or individual‐based water relaxation times. Methods: Spectra were acquired in 33 healthy volunteers (50.1 years, SD = 17.19, 18 females) on a 3 T Philipps MR system using a point‐resolved spectroscopy (PRESS) sequence optimized with very selective saturation pulses (OVERPRESS) and voxel‐based flip angle calibration (effective volume of interest size: 8.8 × 10.2 × 12.2 mm³). Spectra were fitted using LCModel and SNR, NAA peak linewidths and Cramér‐Rao lower bounds (CRLBs) were measured after spectral registration and after minimal frequency alignment. Results: Spectral registration improved SNR by 5% (p = 0.026, median value post‐correction: 18.0) and spectral linewidth by 23% (p < 0.001, 4.3 Hz), and reduced the metabolites' CRLBs by 1% to 15% (p < 0.026). Correlational analyses revealed smaller SNR improvements with greater head motion (p = 0.010) recorded using a markerless motion tracking system. Higher metabolite concentrations were detected using individual‐based compared to literature‐based water relaxation times (p < 0.001). Conclusion: This study demonstrates high‐quality ¹H‐MRS acquisition in the PAG using spectral registration. This shows promise for future ¹H‐MRS studies in the PAG and possibly other clinically relevant brain regions with similar methodological challenges

In situ temperature determination using magnetic resonance spectroscopy thermometry for noninvasive postmortem examinations

Magnetic resonance spectroscopy (MRS) thermometry offers a noninvasive, localized method for estimating temperature by leveraging the temperature‐dependent chemical shift of water relative to a temperature‐stable reference metabolite under suitable calibration. Consequentially, this technique has significant potential as a tool for postmortem MR examinations in forensic medicine and pathology. In these examinations, the deceased are examined at a wide range of body temperatures, and MRS thermometry may be used for the temperature adjustment of magnetic resonance imaging (MRI) protocols or for corrections in the analysis of MRI or MRS data. However, it is not yet clear to what extent postmortem changes may influence temperature estimation with MRS thermometry. In addition, N‐acetylaspartate, which is commonly used as an in vivo reference metabolite, is known to decrease with increasing postmortem interval (PMI). This study shows that lactate, which is not only present in significant amounts postmortem but also has a temperature‐stable chemical shift, can serve as a suitable reference metabolite for postmortem MRS thermometry. Using lactate, temperature estimation in postmortem brain tissue of severed sheep heads was accurate up to 60 h after death, with a mean absolute error of less than 0.5°C. For this purpose, published calibrations intended for in vivo measurements were used. Although postmortem decomposition resulted in severe metabolic changes, no consistent deviations were observed between measurements with an MR‐compatible temperature probe and MRS thermometry with lactate as a reference metabolite. In addition, MRS thermometry was applied to 84 deceased who underwent a MR examination as part of the legal examination. MRS thermometry provided plausible results of brain temperature in comparison with rectal temperature. Even for deceased with a PMI well above 60 h, MRS thermometry still provided reliable readings. The results show a good suitability of MRS thermometry for postmortem examinations in forensic medicine

Ballistic study on the penetration potential and injury potential of different bullet types in the use of a newly developed bullet shooting stunner for adequate stunning of heavy cattle

IntroductionRecently, a special bullet shooting stunner for heavy cattle has been developed that fires a bullet instead of a bolt. In the search for a suitable ammunition, the following criteria must be met: First, the energy of the bullet must be sufficient to penetrate the thick frontal bones of heavy cattle. Second, the injury potential at the corresponding penetration depth should preferably be large in order to damage brain tissue relevant to stunning. Third, the bullet must not perforate the occipital bone (over-penetration).MethodsFour different bullet types [Hornady FTX, Hydra-Shok, Black Mamba, and a common full metal jacket (FMJ) bullet] were evaluated in a series of experiments on soap blocks and removed bone plates followed by computed tomography examinations. Penetration potential was evaluated in terms of kinetic energy relative to the caliber of the bullet, i.e., mean energy density (ED). Injury potential was evaluated by the mean extent of the cavity volume (e$_{CV}$) at the relevant penetration depth of 5.5 to 7.5 cm in the soap block.ResultsAll four bullet types passed through the frontal bone plate. The ED was 17.50 J/mm$^{2}$ (Hornady FTX), 17.46 J/mm$^{2}$ (Hydra-Shok), 13.47 J/mm$^{2}$ (Black Mamba), and 13.47 J/mm$^{2}$ (FMJ). The Hornady FTX and the Hydra-Shok each fragmented heavily. The FMJ was excluded after three experiments due to over-penetrations. The e$_{CV}$ was e$_{CV}$ = 3.77 cm$^{2}$ (Hornady FTX), 2.71 cm$^{2}$ (Hydra-Shok), and 1.31 cm$^{2}$ (Black Mamba), with a significant difference (p = 0.006) between the Hornady FTX and the Black Mamba.DiscussionFor use in heavy cattle, the Hornady FTX and the Hydra-Shok are recommended due to the larger e$_{CV}$ than the Black Mamba

Effects of Psychotherapy on Glutamatergic Neurotransmission

Introduction: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. Methods: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). Results: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. Discussion: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery

Effects of psychotherapy on glutamatergic neurotransmission

Introduction: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. Methods: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). Results: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. Discussion: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery

ERETIC with automatic phase adjustment and eddy current correction compensation

Introduction ERETIC (Electrical REference To access Invivo Concentrations) has proven to be a reliable and accurate method for the quantification of metabolite concentrations in vivo in single voxel MRS Materials and Methods In the setup used here [2] the electrical reference signal is generated by the spectrometer itself. An amplitude modulated RF pulse is sent through an auxiliary channel and transmitted over an optical system to the coil. To avoid lineshape distortions of the ERETIC peak in the eddy current corrected spectra, this RF pulse is modified between the water reference scan and the acquisition of the water suppressed spectra, without prolonging the measurement time. Directly after the water reference scan the time-dependent phase of the complex water signal is calculated at every time point and added to the ERETIC signal by frequency modulation of the RF pulse. In a sense, an inverse Klose correction is thus applied to the ERETIC signal. In the subsequent scan of the water suppressed signal, the ERETIC signal then has the same time-dependent phase distortion as all metabolite signals that experience eddy current effects. To obtain the same zero-order phase for the ERETIC signal as for the water signal (and thus as for the metabolites), the phase of the RF pulse is initially measured and set to zero in an additional preparation step. After that, the phase of the water signal from the reference scan at the first time point is added as a constant phase to the RF pulse. This method was implemented in the control software of a Philips Achieva 3T human MRI scanner (Philips Healthcare, Best, The Netherlands) and validated by performing 10 scans each in the centrum semiovale of two different healthy volunteers, alternatingly with and without the modifications described above. Scan parameters were as follows: TR/TE 2359ms/27ms, 128 spectral averages divided in 8 dynamics, 4 unsuppressed water scans in each dynamic, 25x25x25 mm 3 voxel size using PRESS localization. All signals were corrected for eddy current effects using the Klose approach and fitted using LCModel with simulated basis sets. The ERETIC peak is fitted by simulating a peak with a GaussianLorentzian lineshape using the CHISMU control parameter in LCModel. Results and Discussion With the modifications for the ERETIC signal proposed here, after eddy current correction, the ERETIC peak is automatically in phase with all the other metabolites and shows no line distortion. Therefore the ERETIC peak can be readily fitted with LCModel

Fundamentals of in situ postmortem magnetic resonance spectroscopy of the brain in the forensic framework - a review and outlook

This review contextualizes the collective research on in situ proton postmortem magnetic resonance spectroscopy of the brain and derives the basic approaches for its application in forensic pathology. The basic concepts of magnetic resonance spectroscopy are outlined for a target audience in forensic pathology. A major application of postmortem in situ magnetic resonance spectroscopy is the prediction of the postmortem interval, which has been demonstrated in animal studies. Current research has directly quantified relevant metabolites such as ethanol, glucose, and beta-hydroxybutyrate to draw conclusions for forensic casework. This application is currently limited to a few relevant metabolites. A future potential of postmortem in situ magnetic resonance spectroscopy is the analysis of the entire metabolomic pattern. Estimation of cause of death based on the postmortem metabolome could be the next milestone in postmortem in situ magnetic resonance spectroscopy

Feasibility, technique and accuracy of ultrasound-guided transurethral injections into the urinary sphincter of female cadavers: proof of concept

BACKGROUND: The injection of muscle precursor cells (MPC) into the external urinary sphincter muscle (EUS) is a promising therapeutic option for regenerative treatment of stress urinary incontinence (SUI). The objective of the present project was to conduct a pre-clinical trial to investigate the feasibility and accuracy of ultrasound (US) guided, transurethral injections into the EUS of female cadavers. METHODS: This is a prospective, anatomical, interventional and radiological cadaveric laboratory investigation. Two urologists performed transurethral US-guided injections to deliver nano-iron particles into the EUS. The intervention was performed in three unfixed, fresh female cadavers. Each cadaver received MRI before and CT as well as MRI of the pelvis after the injections. RESULTS: The precision and accumulation of nano-iron particles in the EUS was compared using a rating scale to evaluate left versus right and anterior versus posterior distribution in axial and sagittal orientation with US, MRI and CT. The accuracy of our US-guided injections into the anterior target region yielded 4 points on the rating scale. Adequate precision and accumulation of particles in the left versus right EUS were also demonstrated (3 vs. 3.33 points, respectively). Signal intensity in MRI revealed a mean ratio of 0.33 before and after injection. CT scans showed no relevant artefacts impairing the assessment. CONCLUSION: US-guided, transurethral injection into the EUS is feasible and imaging reveals a precise accumulation in the target region. Our method provides an appropriate approach to deliver MPC in the EUS muscle for a regenerative treatment of SUI in the near future

7-T MRI for brain virtual autopsy: a proof of concept in comparison to 3-T MRI and CT

The detection and assessment of cerebral lesions and traumatic brain injuries are of particular interest in forensic investigations in order to differentiate between natural and traumatic deaths and to reconstruct the course of events in case of traumatic deaths. For this purpose, computed tomography (CT) and magnetic resonance imaging (MRI) are applied to supplement autopsy (traumatic death) or to supplant autopsy (natural deaths). This approach is termed “virtual autopsy.” The value of this approach increases as more microlesions and traumatic brain injuries are detected and assessed. Focusing on these findings, this article describes the examination of two decedents using CT, 3-T, and 7-T MRI. The main question asked was whether there is a benefit in using 7-T over 3-T MRI. To answer this question, the 3-T and 7-T images were graded regarding the detectability and the assessability of coup/contrecoup injuries and microlesions using 3-point Likert scales. While CT missed these findings, they were detectable on 3-T and 7-T MRI. However, the 3-T images appeared blurry in direct comparison with the 7-T images; thus, the detectability and assessability of small findings were hampered on 3-T MRI. The potential benefit of 7-T over 3-T MRI is discussed