What do brain endocasts tell us? A comparative analysis of the accuracy of sulcal identification by experts and perspectives in palaeoanthropology.

Palaeoneurology is a complex field as the object of study, the brain, does not fossilize. Studies rely therefore on the (brain) endocranial cast (often named endocast), the only available and reliable proxy for brain shape, size and details of surface. However, researchers debate whether or not specific marks found on endocasts correspond reliably to particular sulci and/or gyri of the brain that were imprinted in the braincase. The aim of this study is to measure the accuracy of sulcal identification through an experiment that reproduces the conditions that palaeoneurologists face when working with hominin endocasts. We asked 14 experts to manually identify well-known foldings in a proxy endocast that was obtained from an MRI of an actual in vivo Homo sapiens head. We observe clear differences in the results when comparing the non-corrected labels (the original labels proposed by each expert) with the corrected labels. This result illustrates that trying to reconstruct a sulcus following the very general known shape/position in the literature or from a mean specimen may induce a bias when looking at an endocast and trying to follow the marks observed there. We also observe that the identification of sulci appears to be better in the lower part of the endocast compared to the upper part. The results concerning specific anatomical traits have implications for highly debated topics in palaeoanthropology. Endocranial description of fossil specimens should in the future consider the variation in position and shape of sulci in addition to using models of mean brain shape. Moreover, it is clear from this study that researchers can perceive sulcal imprints with reasonably high accuracy, but their correct identification and labelling remains a challenge, particularly when dealing with extinct species for which we lack direct knowledge of the brain.

Dysregulation of energy metabolism in multiple sclerosis measured in vivo with diffusion-weighted spectroscopy.

OBJECTIVE: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS). METHODS: Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine-phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM). Multiple regressions were used to compare metabolite ADCs between groups and to explore clinical correlations. RESULTS: In patients compared with HCs, we found a reduction in ADC(tNAA) in the TGM, reflecting functional and structural neuro-axonal damage, and in ADC(tCr) in both NAWM and TGM, possibly reflecting a reduction in energy supply in neurons and glial cells. Metabolite ADCs did not correlate with tissue atrophy, lesional volume or metabolite concentrations, while in TGM metabolite ADCs correlated with clinical scores. CONCLUSION: DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies.

Ultra-short time-echo based ray tracing for transcranial focused ultrasound aberration correction in human calvaria.

OBJECTIVE: Magnetic resonance guided transcranial focused ultrasound holds great promises for treating neurological disorders. This technique relies on skull aberration correction which requires computed tomography (CT) scans of the skull of the patients. Recently, ultra-short time-echo (UTE) magnetic resonance (MR) sequences have unleashed the MRI potential to reveal internal bone structures. In this study, we measure the efficacy of transcranial aberration correction using UTE images. Approach. We compare the efficacy of transcranial aberration correction using UTE scans to CT based correction on four skulls and two targets using a clinical device (Exablate Neuro, Insightec, Israel). We also evaluate the performance of a custom ray tracing algorithm using both UTE and CT estimates of acoustic properties and compare these against the performance of the manufacturer's proprietary aberration correction software. Main results. UTE estimated skull maps in Hounsfield units (HU) had a mean absolute error of 242 ± 20 HU (n=4). The UTE skull maps were sufficiently accurate to improve pressure at the target (no correction: 0.44 ± 0.10, UTE correction: 0.79 ± 0.05, manufacturer CT: 0.80 ± 0.05), pressure confinement ratios (no correction: 0.45 ± 0.10, UTE correction: 0.80 ± 0.05, manufacturer CT: 0.81 ± 0.05), and targeting error (no correction: 1.06 ± 0.42 mm, UTE correction 0.30 ± 0.23 mm, manufacturer CT: 0.32 ± 0.22) (n=8 for all values). When using CT, our ray tracing algorithm performed slightly better than UTE based correction with pressure at the target (UTE: 0.79 ± 0.05, CT: 0.84 ± 0.04), pressure confinement ratios (UTE: 0.80 ± 0.05, CT: 0.84 ± 0.04), and targeting error (UTE: 0.30 ± 0.23 mm, CT: 0.17 ± 0.15). Significance. These 3D transcranial measurements suggest that UTE sequences could replace CT scans in the case of MR guided focused ultrasound with minimal reduction in performance which will avoid ionizing radiation exposure to the patients and reduce procedure time and cost. .

Sustained reduction of essential tremor with low-power non-thermal transcranial focused ultrasound stimulations in humans.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique; when skull aberrations are compensated for, this technique allows, with millimetric accuracy, circumvention of the invasive surgical procedure associated with deep brain stimulation (DBS) and the limited spatial specificity of transcranial magnetic stimulation. OBJECTIVE: /hypothesis: We hypothesize that MR-guided low-power TUS can induce a sustained decrease of tremor power in patients suffering from medically refractive essential tremor. METHODS: The dominant hand only was targeted, and two anatomical sites were sonicated in this exploratory study: the ventral intermediate nucleus of the thalamus (VIM) and the dentato-rubro-thalamic tract (DRT). Patients (N = 9) were equipped with MR-compatible accelerometers attached to their hands to monitor their tremor in real-time during TUS. RESULTS: VIM neurostimulations followed by a low-duty cycle (5 %) DRT stimulation induced a substantial decrease in the tremor power in four patients, with a minimum of 89.9 % reduction when compared with the baseline power a few minutes after the DRT stimulation. The only patient stimulated in the VIM only and with a low duty cycle (5 %) also experienced a sustained reduction of the tremor (up to 93.4 %). Four patients (N = 4) did not respond. The temperature at target was 37.2 ± 1.4 °C compared to 36.8 ± 1.4 °C for a 3 cm away control point. CONCLUSIONS: MR-guided low power TUS can induce a substantial and sustained decrease of tremor power. Follow-up studies need to be conducted to reproduce the effect and better to understand the variability of the response amongst patients. MR thermometry during neurostimulations showed no significant thermal rise, supporting a mechanical effect.