Case report: Utilizing diffusion-weighted MRI on a patient with chronic low back pain treated with spinal cord stimulation

Diffusion-weighted magnetic resonance imaging (dwMRI) has increasingly demonstrated greater utility in analyzing neuronal microstructure. In patients with chronic low back pain (cLBP), using dwMRI to observe neuronal microstructure can lead to non-invasive biomarkers which could provide clinicians with an objective quantitative prognostic tool. In this case report, we investigated dwMRI for the development of non-invasive biomarkers by conducting a region-based analysis of a 55-year-old male patient with failed back surgery syndrome (FBSS) treated with spinal cord stimulation (SCS). We hypothesized that dwMRI could safely generate quantitative data reflecting cerebral microstructural alterations driven by neuromodulation. Neuroimaging was performed at 6- and 12- months post-SCS implantation. The quantitative maps generated included diffusion tensor imaging (DTI) parameters; fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) computed from whole brain tractography. To examine specific areas of the brain, 44 regions of interest (ROIs), collectively representing the pain NeuroMatrix, were extracted and registered to the patient's diffusion space. Average diffusion indices were calculated from the ROIs at both 6- and 12- months. Regions with >10% relative change in at least 3 of the 4 maps were reported. Using this selection criterion, 8 ROIs demonstrated over 10% relative changes. These ROIs were mainly located in the insular gyri. In addition to the quantitative data, a series of questionnaires were administered during the 6- and 12-month visits to assess pain intensity, functional disability, and quality of life. Overall improvements were observed in these components, with the Pain Catastrophizing Scale (PCS) displaying the greatest change. Lastly, we demonstrated the safety of dwMRI for a patient with SCS. In summary, the results from the case report prompt further investigation in applying dwMRI in a larger cohort to better correlate the influence of SCS with brain microstructural alterations, supporting the utility of dwMRI to generate non-invasive biomarkers for prognostication

Exploring Functional Connectivity in Chronic Spinal Cord Injury Patients With Neuropathic Pain Versus Without Neuropathic Pain

The great majority of spinal cord injury (SCI) patients have debilitating chronic pain. Despite decades of research, these pain pathways of neuropathic pain (NP) are unknown. SCI patients have been shown to have abnormal brain pain pathways. We hypothesize that SCI NP patients’ pain matrix is altered compared to SCI patients without NP. This study examines the functional connectivity (FC) in SCI patients with moderate-severe chronic NP compared to SCI patients with mild-no NP. These groups were compared to control subjects. The Neuropathic Pain Questionnaire and neurological evaluation based on the International Standard Neurological Classification of SCI were utilized to define the severity and level of injury. Of the 10 SCI patients, 7 (48.6 ± 17.02 years old, 6 male and 1 female) indicated that they had NP and 3 did not have NP (39.33 ± 8.08 years old, 2 male and 1 female). Ten uninjured neurologically intact participants were used as controls (24.8 ± 4.61 years old, 5 male and 5 female). FC metrics were obtained from the comparisons of resting-state functional magnetic resonance imaging among our various groups (controls, SCI with NP, and SCI without NP). For each comparison, a region-of-interest (ROI)-to-ROI connectivity analysis was pursued, encompassing a total of 175 ROIs based on a customized atlas derived from the AAL3 atlas. The analysis accounted for covariates such as age and sex. To correct for multiple comparisons, a strict Bonferroni correction was applied with a significance level of p \u3c 0.05/NROIs. When comparing SCI patients with moderate-to-severe pain to those with mild-to-no pain, specific thalamic nuclei had altered connections. These nuclei included: medial pulvinar; lateral pulvinar; medial geniculate nucleus; lateral geniculate nucleus; and mediodorsal magnocellular nucleus. There was increased FC between the lateral geniculate nucleus and the anteroventral nucleus in NP post-SCI. Our analysis additionally highlights the relationships between the frontal lobe and temporal lobe with pain. This study successfully identifies thalamic neuroplastic changes that occur in patients with SCI who develop NP. It additionally underscores the pain matrix and involvement of the frontal and temporal lobes as well. Our findings complement that the development of NP post-SCI involves cognitive, emotional, and behavioral influences

The Impact of Mechanical Thrombectomy on the Blood-Brain Barrier in Patients With Acute Ischemic Stroke: A Non-contrast MR Imaging Study Using DP-pCASL and NODDI

Background and purpose: While mechanical thrombectomy (MT) achieves restoration of cerebral blood flow to the area at risk in patients with acute ischemic stroke (AIS), the influx of blood flow may exacerbate the blood-brain barrier (BBB) disruption and extravasation across the BBB, and it therefore remains unclear how reperfusion impacts the blood-brain barrier integrity. In this study, we use diffusion-prepared pseudocontinuous ASL (DP-pCASL) and Neurite Orientation Dispersion and Density Imaging (NODDI) sequence to measure the water exchange rate (kw) in patients who underwent either MT or medical management and determine its impact on the brain tissue microstructure in order to elucidate the impact of MT on BBB complex integrity. Materials and methods: We prospectively enrolled 21 patients with AIS treated at our institution from 10/2021 to 6/2023 who underwent MR imaging at a 3.0-Tesla scanner. Patients underwent DP-pCASl and NODDI imaging in addition to the standard stroke protocol which generated cerebral blood flow (CBF), arterial transit time (ATT), water exchange rate (kw), orientation dispersion index (ODI), intracellular volume fraction (ICVF), and free water fraction (FWF) parametric maps. Results: Of the 21 patients, 11 underwent MT and 10 were treated non-operatively. The average age and NIHSS for the MT cohort and non-MT cohorts were 69.3 ± 16.6 years old and 15.0 (12.0-20.0), and 70.2 ± 10.7 (p = 0.882) and 6.0 (3.8-9.0, p = 0.003) respectively. The average CBF, ATT, and kw in the infarcted territory of the MT cohort were 38.2 (18.4-59.6), 1347.6 (1182.5-1842.3), and 107.8 (79.2-140.1) respectively. The average CBF, ATT, and kw in the stroke ROI were 16.0 (8.8-36.6, p = 0.036), 1090.8 (937.1-1258.9, p = 0.013), 89.7 (68.0-122.7, p = 0.314) respectively. Linear regression analysis showed increasing CBF (p = 0.008) and undergoing mechanical thrombectomy (p = 0.048) were significant predictors of increased kw. Conclusion: Using our multimodal non-contrast MRI protocol, we demonstrate that increased CBF and mechanical thrombectomy increased kw, suggesting a better functioning BBB complex. Higher kw suggests less disruption of the BBB complex in the MT cohort

Case Report: The Promising Application of Dynamic Functional Connectivity Analysis on an Individual With Failed Back Surgery Syndrome

Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional connectivity (FC) was performed on the rsfMRI data acquired from the FBSS subject, and then compared to a group of 17 healthy controls. Seeds were identified by an atlas of resting state networks (RSNs), which is composed of 32 regions grouped into 8 networks. Sliding-window method and k-means clustering were used in dynamic FC analysis, which resulted in 4 brain states for each group. Our results demonstrated the safety and feasibility of 3T MRI scanning in a patient with implanted SCS system. Compared to the brain states of healthy controls, the FBSS subject presented very different FC patterns in less frequent brain states. The mean dwell time of brain states showed distinct distributions: the FBSS subject seemed to prefer a single state over the others. Although future studies with large sample sizes are needed to make statistical conclusions, our findings demonstrated the promising application of dynamic FC to provide more granularity with FC changes associated with different brain states in chronic pain

Amplitude Synchronization of Spontaneous Activity of Medial and Lateral Temporal Gyri Reveals Altered Thalamic Connectivity in Patients With Temporal Lobe Epilepsy

In this study, we examined whether amplitude synchronization of medial (MTL) and lateral (LTL) temporal lobes can detect unique alterations in patients with MTL epilepsy (mTLE) with mesial temporal sclerosis (MTS). This was a retrospective study of preoperative resting-state fMRI (rsfMRI) data from 31 patients with mTLE with MTS (age 23-69) and 16 controls (age 21-35). fMRI data were preprocessed based on a multistep preprocessing pipeline and registered to a standard space. Using each subject\u27s T1-weighted scan, the MTL and LTL were automatically segmented, manually revised and then fit to a standard space using a symmetric normalization registration algorithm. Dual regression analysis was applied on preprocessed rsfMRI data to detect amplitude synchronization of medial and lateral temporal segments with the rest of the brain. We calculated the overlapped volume ratio of synchronized voxels within specific target regions including the thalamus (total and bilateral). A general linear model was used with Bonferroni correction for covariates of epilepsy duration and age of patient at scan to statistically compare synchronization in patients with mTLE with MTS and controls, as well as with respect to whether patients remained seizure-free (SF) or not (NSF) after receiving epilepsy surgery. We found increased ipsilateral positive connectivity between the LTLs and the thalamus and contralateral negative connectivity between the MTLs and the thalamus in patients with mTLE with MTS compared to controls. We also found increased asymmetry of functional connectivity between temporal lobe subregions and the thalamus in patients with mTLE with MTS, with increased positive connectivity between the LTL and the lesional-side thalamus as well as increased negative connectivity between the MTL and the nonlesional-side thalamus. This asymmetry was also seen in NSF patients but was not seen in SF patients and controls. Amplitude synchronization was an effective method to detect functional connectivity alterations in patients with mTLE with MTS. Patients with mTLE with MTS overall showed increased temporal-thalamic connectivity. There was increased functional involvement of the thalamus in MTS, underscoring its role in seizure spread. Increased functional thalamic asymmetry patterns in NSF patients may have a potential role in prognosticating patient response to surgery. Elucidating regions with altered functional connectivity to temporal regions can improve understanding of the involvement of different regions in the disease to potentially target for intervention or use for prognosis for surgery. Future studies are needed to examine the effectiveness of using patient-specific abnormalities in patterns to predict surgical outcome

The impact of mechanical thrombectomy on the blood–brain barrier in patients with acute ischemic stroke: A non-contrast MR imaging study using DP-pCASL and NODDI

Background and purpose: While mechanical thrombectomy (MT) achieves restoration of cerebral blood flow to the area at risk in patients with acute ischemic stroke (AIS), the influx of blood flow may exacerbate the blood–brain barrier (BBB) disruption and extravasation across the BBB, and it therefore remains unclear how reperfusion impacts the blood–brain barrier integrity. In this study, we use diffusion-prepared pseudocontinuous ASL (DP-pCASL) and Neurite Orientation Dispersion and Density Imaging (NODDI) sequence to measure the water exchange rate (kw) in patients who underwent either MT or medical management and determine its impact on the brain tissue microstructure in order to elucidate the impact of MT on BBB complex integrity. Materials and methods: We prospectively enrolled 21 patients with AIS treated at our institution from 10/2021 to 6/2023 who underwent MR imaging at a 3.0-Tesla scanner. Patients underwent DP-pCASl and NODDI imaging in addition to the standard stroke protocol which generated cerebral blood flow (CBF), arterial transit time (ATT), water exchange rate (kw), orientation dispersion index (ODI), intracellular volume fraction (ICVF), and free water fraction (FWF) parametric maps. Results: Of the 21 patients, 11 underwent MT and 10 were treated non-operatively. The average age and NIHSS for the MT cohort and non-MT cohorts were 69.3 ± 16.6 years old and 15.0 (12.0–20.0), and 70.2 ± 10.7 (p = 0.882) and 6.0 (3.8–9.0, p = 0.003) respectively. The average CBF, ATT, and kw in the infarcted territory of the MT cohort were 38.2 (18.4–59.6), 1347.6 (1182.5–1842.3), and 107.8 (79.2–140.1) respectively. The average CBF, ATT, and kw in the stroke ROI were 16.0 (8.8–36.6, p = 0.036), 1090.8 (937.1–1258.9, p = 0.013), 89.7 (68.0–122.7, p = 0.314) respectively. Linear regression analysis showed increasing CBF (p = 0.008) and undergoing mechanical thrombectomy (p = 0.048) were significant predictors of increased kw. Conclusion: Using our multimodal non-contrast MRI protocol, we demonstrate that increased CBF and mechanical thrombectomy increased kw, suggesting a better functioning BBB complex. Higher kw suggests less disruption of the BBB complex in the MT cohort