3D reconstruction techniques of human coronary bifurcations for shear stress computations

Background

Heterogeneity in plaque composition in human coronary artery bifurcations is associated with blood flow induced shear stress. Shear stress is generally determined by combing 3D lumen data and computational fluid dynamics (CFD). We investigated two new procedures to generate 3D lumen reconstructions of coronary artery bifurcations for shear stress computations.

Methods

We imaged 10 patients with multislice computer tomography (MSCT) and intravascular ultrasound (IVUS). The 3D reconstruction of the main branch was based on the fusion of MSCT and IVUS. The proximal part of side branch was reconstructed using IVUS data or MSCT data, resulting in two different reconstructions of the bifurcation region. The distal part of the side branch was based on MSCT data alone. The reconstructed lumen was combined with CFD to determine the shear stress. Low and high shear stress regions were defined and shear stress patterns in the bifurcation regions were investigated.

Results

The 3D coronary bifurcations were successfully generated with both reconstruction procedures. The geometrical features of the bifurcation region for the two reconstruction procedures did not reveal appreciable differences. The shear stress maps showed a qualitative agreement, and the low and high shear stress regions were similar in size and average shear stress values were identical. The low and high shear stress regions showed an overlap of approximately 75%.

Conclusion

Reconstruction of the side branch with MSCT data alone is an adequate technique to study shear stress and wall thickness in the bifurcation region. The reconstruction procedure can be applied to further investigate the effect of shear stress on atherosclerosis in coronary bifurcations.     

A new imaging technique to study 3-D plaque and shear stress distribution in human coronary artery bifurcations in vivo

OBJECTIVE: Bifurcations of coronary arteries are predilection sites for atherosclerosis and expansive remodeling, the latter being associated with plaque vulnerability. Both are related to blood flow-induced shear stress (SS). We present a new approach to generate 3-D reconstructions of coronary artery bifurcations in vivo and investigate the relationship between SS, wall thickness (WT) and remodeling. METHODS: The patient specific 3-D reconstruction of the main branch of the bifurcation was obtained by combining intravascular ultrasound and biplane angiography, and the 3-D lumen of the side branch was based on biplane angiography only. The two data sets were fused and computational methods were applied to determine the SS distribution, using patient derived flow and viscosity data. The intravascular ultrasound data allowed us to measure local WT and remodeling in the main branch. RESULTS: The lumen reconstruction procedure was successful and it was shown that the impact of the side branch on SS distribution in the main branch diminished within 3mm. Distal to the bifurcation, two continuous regions in the main branch were identified. In the proximal region, we observed lumen preservation, and expansive remodeling. Although a plaque was observed in the low SS region at the non-divider wall, no relationship between SS and WT was found. In the distal region, we observed lumen narrowing and a significant positive relationship between SS and WT. CONCLUSIONS: A new imaging technique was applied to generate a 3-D reconstruction of a human coronary artery bifurcation in vivo. The observed relationship between SS, WT and remodeling in this specific patient illustrates the spatial heterogeneity of the atherosclerosis in the vicinity of arterial bifurcations.     

Sex differences in intracranial arterial bifurcations

Background: Subarachnoid hemorrhage (SAH) is a serious condition, occurring more frequently in females than in males. SAH is mainly caused by rupture of an intracranial aneurysm, which is formed by localized dilation of the intracranial arterial vessel wall, usually at the apex of the arterial bifurcation. The female preponderance is usually explained by systemic factors (hormonal influences and intrinsic wall weakness); however, the uneven sex distribution of intracranial aneurysms suggests a possible physiologic factor—a local sex difference in the intracranial arteries.Objective: The aim of this study was to explore sex variation in the bifurcation anatomy of the middle cerebral artery (MCA) and internal carotid artery (ICA), and the subsequent hemodynamic impact.Methods: Vessel radii and bifurcation angles were measured in patients with MCA and ICA bifurcations. Data from a previously published study of 55 patients undergoing diagnostic cerebral digital subtraction angiography at Dalcross Private Hospital in Sydney, Australia, between 2002 and 2003, were available for analysis. The measurements were used to create idealized, averaged bifurcations of the MCA and ICA for females and males. Computational fluid dynamics simulations were performed to calculate hemodynamic forces in the models.Results: The vessel radii and bifurcation angles of 47 MCA and 52 ICA bifurcations in 49 patients (32 females, 17 males; mean age, 53 years; age range, 14–86 years) were measured. Statistically significant sex differences were found in vessel diameter (males larger than females; P < 0.05), but not in bifurcation angle. Computational fluid dynamics simulations revealed higher wall shear stress in the female MCA (19%) and ICA (50%) bifurcations compared with the male bifurcations.Conclusions: This study of MCA and ICA bifurcations in female and male patients suggests that sex differences in vessel size and blood flow velocity result in higher hemodynamic forces acting on the vessel wall in females. This new hypothesis may partly explain why intracranial aneurysms and SAH are more likely to occur in females than in males.     

Effects of intra-coronary administration of leukotriene D4 in the anaesthetized dog

The left anterior descending coronary artery in anaesthetized greyhounds was perfused at constant pressure with blood pumped from the carotid artery. Phasic and mean coronary flow, left ventricular pressure, dP/dt, cardiac output, ECG, heart rate and systemic pressure were measured. Leukotriene (LT) D₄ was administered into the left anterior descending coronary artery as a bolus injection. LTD₄ caused dose-related reductions in coronary flow. Other parameters showed little immediate change although a gradual decrease in left ventricular pressure, dP/dt, cardiac output and systemic pressure occurred after administration of LTD₄. Following intracoronary administration of LTD₄ small surface haemorrhages were observed over the area perfused. The reduction in coronary flow was not inhibited by indomethacin.     

Hemodynamic impacts of various types of stenosis in the left coronary artery bifurcation: A patient-specific analysis

This study investigates the hemodynamic changes to various types of coronary stenosis in the left coronary artery bifurcation, based on a patient-specific analysis. Twenty two patients with left coronary artery disease were included in this study. All stenoses involving the left coronary artery bifurcation were classified into four types, according to their locations: A) left circumflex (LCx) and left anterior descending (LAD), B) LCx only, C) left main stem only, and D) LAD only. Computational fluid dynamics (CFD) was performed to analyze the flow and wall shear stress (WSS) changes in all reconstructed left coronary geometries. Our results showed that the flow velocity and WSS were significantly increased at stenotic locations. High WSS was found at >70% lumen stenosis, which ranged from 2.5 Pa to 3.5 Pa. This study demonstrates that in patients with more than 50% stenosis in the left coronary artery bifurcation, WSS plays an important role in providing information about the extent of coronary atherosclerosis in the left coronary artery branch.     

ETB-mediated contraction differs between left descending coronary artery and its next branch

Pig left descending coronary artery (main artery) and its next branch (branch arteries) differ in many properties. Here we report on the receptor types and the Ca²⁺ pools utilized for endothelin (ET) contraction in 3 mm long de-endothelialized rings of the main (weight 7.38 ± 0.38 mg) and the branch (1.07 ± 0.03 mg) arteries. KCl (60 mM) contracted the main and the branch arteries with force of 41.8 ± 3.1 and 16.9 ± 1.0 mN (millinewton), respectively. Force of contraction for all the other agents was normalized taking the KCl value as 100%. We determined the total ET-induced responses using ET-1 and those mediated by ET_B using IRL1620. In Ca²⁺-containing solutions, ET-1 contracted the main arteries with pEC_B = 8.2 ± 0.1 and a maximum force of 98 ± 5%. The branch arteries also gave similar values of pEC₅₀ (8.4 ± 0.1) and maximum force (99 ± 14%). IRL1620 contracted the main and the branch arteries with pEC₅₀ = 7.9 ± 0.1 but the maximum force was significantly higher in the branch arteries (44 ± 3%) than in the main (15 ± 2%). In Ca²⁺-free solutions, the pEC₅₀ values for ET-1 or IRL-1620 did not change but the maximum force of contraction was diminished considerably in both main and branch arteries. Thus, the left coronary artery and its next branch differ in that the role of ET_B receptors is greater in the latter.     

Numerical Analysis of Blood Flow through COVID-19 Infected Arteries

Computational Fluid Dynamics has become relevant in the study of hemodynamics, where clinical results are challenging to obtain. This paper discusses a 2-Dimensional transient blood flow analysis through an arterial bifurcation for patients infected with the Coronavirus. The geometry considered is an arterial bifurcation with main stem diameter 3 mm and two outlets. The left outlet (smaller) has a diameter of 1.5 mm and the right outlet (larger), 2 mm. The length of the main stem, left branch and right branch are fixed at 35 mm, 20 mm and 25 mm respectively. Viscosity change that occurs in the blood leads to different parametrical changes in blood flow. The blood flow towards the smaller branch is significantly affected by the changed blood viscosity. Extended regions of high pressure and increased velocity towards the larger outlet are obtained. The Time Averaged Wall Shear Stress (TAWSS) for the corona affected artery is found to be 10.4114 Pa at a 90° angle of bifurcation as compared to 2.45002 Pa of the normal artery. For varying angles of bifurcation, an angle of 75° was found to have a maximum Time Averaged Wall Shear Stress of 2.46076 Pa and 10.42542 Pa for normal and corona affected artery, respectively.     

Which diameter and angle rule provides optimal flow patterns in a coronary bifurcation?

The branching angle and diameter ratio in epicardial coronary artery bifurcations are two important determinants of atherogenesis. Murray's cubed diameter law and bifurcation angle have been assumed to yield optimal flows through a bifurcation. In contrast, we have recently shown a 7/3 diameter law (HK diameter model), based on minimum energy hypothesis in an entire tree structure. Here, we derive a bifurcation angle rule corresponding to the HK diameter model and critically evaluate the streamline flow through HK and Murray-type bifurcations. The bifurcations from coronary casts were found to obey the HK diameter model and angle rule much more than Murray's model. A finite element model was used to investigate flow patterns for coronary artery bifurcations of various types. The inlet velocity and pressure boundary conditions were measured by ComboWire. Y-bifurcation of Murray type decreased wall shear stress-WSS (10%-40%) and created an increased oscillatory shear index-OSI in atherosclerosis-prone regions as compared with HK-type bifurcations. The HK-type bifurcations were found to have more optimal flow patterns (i.e., higher WSS and lower OSI) than Murray-type bifurcations which have been traditionally believed to be optimized. This study has implications for changes in bifurcation angles and diameters in percutaneous coronary intervention.     

Healthy and diseased coronary bifurcation geometries influence near-wall and intravascular flow: A computational exploration of the hemodynamic risk

Local hemodynamics has been identified as one main determinant in the onset and progression of atherosclerotic lesions at coronary bifurcations. Starting from the observation that atherosensitive hemodynamic conditions in arterial bifurcation are majorly determined by the underlying anatomy, the aim of the present study is to investigate how peculiar coronary bifurcation anatomical features influence near-wall and intravascular flow patterns. Different bifurcation angles and cardiac curvatures were varied in population-based, idealized models of both stenosed and unstenosed bifurcations, representing the left anterior descending (LAD) coronary artery with its diagonal branch. Local hemodynamics was analyzed in terms of helical flow and exposure to low/oscillatory shear stress by performing computational fluid dynamics simulations.Results show that bifurcation angle impacts lowly hemodynamics in both stenosed and unstenosed cases. Instead, curvature radius influences the generation and transport of helical flow structures, with smaller cardiac curvature radius associated to higher helicity intensity. Stenosed bifurcation models exhibit helicity intensity values one order of magnitude higher than the corresponding unstenosed cases. Cardiac curvature radius moderately affects near-wall hemodynamics of the stenosed cases, with smaller curvature radius leading to higher exposure to low shear stress and lower exposure to oscillatory shear stress. In conclusion, the proposed controlled benchmark allows investigating the effect of various geometrical features on local hemodynamics at the LAD/diagonal bifurcation, highlighting that cardiac curvature influences near wall and intravascular hemodynamics, while bifurcation angle has a minor effect.     

Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole,benzofuran, and benzothiophene analogs of L-741,626

A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D_2-like dopamine receptors. These compounds share structural elements with the classical D_2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4-(4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (6) and 4-(4-iodophenyl)-1-((5-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D₂ versus D₃ receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D₂ binding affinity and the D₂ versus D₃ selectivity.     

Evaluation of the motion of lung tumors during stereotactic body radiation therapy (SBRT) with four-dimensional computed tomography (4DCT) using real-time tumor-tracking radiotherapy system (RTRT)

PurposeWe investigated the usefulness of four-dimensional computed tomography (4DCT) performed before stereotactic body radiation therapy (SBRT) in determining the internal margins for peripheral lung tumors.Methods and MaterialsThe amplitude of the movement of a fiducial marker near a lung tumor measured using the maximum intensity projection (MIP) method in 4DCT imaging was acquired before the SBRT (Amp_CT) and compared with the mean amplitude of the marker movement during SBRT (Amp_mean) and with the maximum amplitude of the marker movement during SBRT (Amp_max) using a real-time tumor-tracking radiotherapy (RTRT) system with 22 patients.ResultsThere were no significant differences between the means of the Amp_mean and the means of the Amp_CT in all directions (LR, P = 0.45; CC, P = 0.80; AP, P = 0.65). The means of the Amp_max were significantly larger than the means of the Amp_CT in all directions (LR, P < 0.01; CC, P = 0.03; AP, P < 0.01). In the lower lobe, the mean difference of the Amp_CT from the mean of the Amp_max was 5.7 ± 8.0 mm, 12.5 ± 16.7 mm, and 6.8 ± 8.5 mm in the LR, CC, and AP directions, respectively.ConclusionsAcquiring 4DCT MIP images before the SBRT treatment is useful to establish the mean amplitude for a patient during SBRT but it underestimates the maximum amplitude during actual SBRT. Caution must be paid to determine the margin with the 4DCT especially for tumors at the lower lobe where it is of the potentially greatest benefit.     

Flow investigations in a model of a three-dimensional human artery with Newtonian and non-Newtonian fluids. Part I

Together with biochemical factors, fluid mechanical factors play a role in atherogenesis and the deposition of blood platelets at bends and bifurcations in human arteries. Hence, flow patterns were investigated in a simplified 3-dimensional model of a human renal artery bifurcation using Newtonian (aqueous glycerol) and non-Newtonian (aqueous solution of polyacrylamide) fluids. Studies were carried out in steady as well as pulsatile flow at inflow Reynolds numbers of 498 and 951 with flow rate ratios main tube V1: right branch V4: left branch V3 of 1: 0.25: 0.25 and 1: 0.18: 0.18 respectively. The velocity distribution proximal and distal to the bifurcations was measured using a laser-Doppler anemometer. In steady flow, zones of flow separation and reverse flow were observed distal to the bifurcations. In pulsatile flow using non-Newtonian fluids, there was a significant enlargement of these zones. Differences between the Newtonian and non-Newtonian fluids occurred especially distal to the bifurcations. Shear stresses along all measuring positions were computed from the velocity gradients.     

Evaluating the accuracy of geometrical distortion correction of magnetic resonance images for use in intracranial brain tumor radiotherapy

AimDetermine the 1) effectiveness of correction for gradient-non-linearity and susceptibility effects on both QUASAR GRID^3D and CIRS phantoms; and 2) the magnitude and location of regions of residual distortion before and after correction.BackgroundUsing magnetic resonance imaging (MRI) as a primary dataset for radiotherapy planning requires correction for geometrical distortion and non-uniform intensity.Materials and MethodsPhantom Study: MRI, computed tomography (CT) and cone beam CT images of QUASAR GRID^3D and CIRS head phantoms were acquired. Patient Study: Ten patients were MRI-scanned for stereotactic radiosurgery treatment. Correction algorithm: Two magnitude and one phase difference image were acquired to create a field map. A MATLAB program was used to calculate geometrical distortion in the frequency encoding direction, and 3D interpolation was applied to resize it to match 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images. MPRAGE images were warped according to the interpolated field map in the frequency encoding direction. The corrected and uncorrected MRI images were fused, deformable registered, and a difference distortion map generated.ResultsMaximum deviation improvements: GRID^3D, 0.27 mm y-direction, 0.07 mm z-direction, 0.23 mm x-direction. CIRS, 0.34 mm, 0.1 mm and 0.09 mm at 20-, 40- and 60-mm diameters from the isocenter. Patient data show corrections from 0.2 to 1.2 mm, based on location. The most-distorted areas are around air cavities, e.g. sinuses.ConclusionsThe phantom data show the validity of our fast distortion correction algorithm. Patient-specific data are acquired in <2 min and analyzed and available for planning in less than a minute.     

6-(4-Benzylpiperazin-1-yl)benzodioxanes as selective ligands at cloned primate dopamine D4 receptors

A series of novel 6-(4-benzylpiperazin-1-yl)benzodioxanes were prepared and screened at selected dopamine receptor subtypes. 6-(4-[4-Chlorobenzyl]piperazin-1-yl)benzodioxane (2d) had high affinity and selectivity for the D₄ dopamine receptor subtype and was identified as a D₄ antagonist via its attenuation of dopamine-induced GTPγ³⁵S binding at the D₄ receptor.     

血清同型半胱氨酸、高敏C反应蛋白及肱踝脉搏波传导速度与冠心病患者冠脉病变程度的相关性研究

目的:探讨血清同型半胱氨酸(Hcy)、高敏C反应蛋白(hs-CRP)及肱踝脉搏波传导速度(baPWV)与冠心病患者冠脉病变程度的相关性。方法:选取2015年6月-2017年10月期间承德医学院附属医院收治的疑似冠心病的患者324例为研究对象,根据冠状动脉造影结果分为冠心病组213例与非冠心病组111例,根据不同冠脉病变程度将冠心病组分为单支病变组87例,双支病变组74例,多支病变组52例,检测并对比所有患者血清Hcy、hs-CRP水平及baPWV值,分析Hcy、hs-CRP水平及baPWV值与冠心病患者冠脉病变程度相关性。结果:冠心病组患者血清Hcy、hs-CRP水平及baPWV值较非冠心病组升高(P0.05)。冠心病组不同冠脉病变程度患者血清Hcy、hs-CRP水平及baPWV值整体比较差异有统计学意义(P0.05),多支病变组与双支病变组患者血清Hcy、hs-CRP水平及baPWV值高于单支病变组,且多支病变组高于双支病变组,差异有统计学意义(P0.05)。经Pearson相关性分析显示,Hcy、hs-CRP及baPWV均与冠心病患者冠脉病变程度呈正相关(P0.05)。结论:冠心病患者血清Hcy、hs-CRP水平及baPWV值高于非冠心病者,且血清Hcy、hs-CRP水平及baPWV值随着冠心病患者冠脉病变程度的加重而升高,与冠脉病变程度呈正相关。     

Contractile activities of leukotrienes C4 and D4 on vascular strips from rabbits

Leukotrienes C₄ (LTC₄) and D₄ (LTD₄), major components of slow-reacting substances of anaphylaxis (SRS-A), caused dose-dependent contractions of rabbit coronary arteries in concentrations of 10^?9 to 10^?7 M and 10^?10 to 10^?7 M, respectively. The potency of LTC₄ and LTD₄, when compared with the concentration that elicits half of the contraction induced by 25 mM KCl, was 17 and 76 times, respectively, greater than that of histamine. In contrast, other blood vessels from rabbits were either unresponsive (renal artery and vein, mesenteric artery and thoracic aorta) or only weakly responsive (pulmonary artery and vein and portal vein) to both leukotrienes even at 10^?7 M. The LTD₄-induced coronary contraction was inhibited by FPL 55712 (10^?7 and 10^?6 M), a selective SRS-A inhibitor, in a dose-dependent manner, but not by diphenhydramine (10^?7 M), a histamine H₁-receptor blocker or by indomethacin (10^?5 M), a prostaglandin synthetase inhibitor, suggesting that LTD₄ has a direct effect on the coronary arteries. These results indicate that the leukotrienes may act as potent, selective coronary vasoconstrictors and that SRS-A responsive receptors exist in the rabbit coronary artery.     

Measurement of coronary bifurcation angle with coronary CT angiography: A phantom study

PurposeAccurate determination of the bifurcation angle and correlation with plaque buildup may lead to the prediction of coronary artery disease (CAD). This work evaluates two techniques to measure bifurcation angles in 3D space using coronary computed tomography angiography (CCTA).Materials and MethodsNine phantoms were fabricated with different bifurcation angles ranging from 55.3° to 134.5°. General X-ray and CCTA were employed to acquire 2D and 3D images of the bifurcation phantoms, respectively. Multiplanar reformation (MPR) and volume rendering technique (VRT) were used to measure the bifurcation angle between the left anterior descending (LAD) and left circumflex arteries (LCx). The measured angles were compared with the true values to determine the accuracy of each measurement technique. Inter-observer variability was evaluated. The two techniques were further applied on 50 clinical CCTA cases to verify its clinical value.ResultsIn the phantom setting, the mean absolute differences calculated between the true and measured angles by MPR and VRT were 2.4° ± 2.2° and 3.8° ± 2.9°, respectively. Strong correlation was found between the true and measured bifurcation angles. Furthermore, no significant differences were found between the bifurcation angles measured using either technique. In clinical settings, large difference of 12.0° ± 10.6° was found between the two techniques.ConclusionIn the phantom setting, both techniques demonstrated a significant correlation to the true bifurcation angle. Despite the lack of agreement of the two techniques in the clinical context, our findings in phantoms suggest that MPR should be preferred to VRT for the measurement of coronary bifurcation angle by CCTA.     

男性内源性性激素水平与冠心病范围及左心室射血分数的相关性

摘要 目的：探究男性内源性性激素水平与冠心病范围及左心室射血分数（LVEF）的相关性。方法：将2018年6月至2020年6月于我院接受治疗的96例经冠状动脉造影术（CAG）确诊为冠心病的96例患者纳入研究,按照临床分型将其区分为稳定型心绞痛（SAP,30例）、不稳定型心绞痛（UAP,30例）、急性心肌梗死（AMI,36例）,另选同期CAG检测结果提示冠状动脉管腔直径狭窄率<50 %的50例个体为对照组,检测入组对象的睾酮（Ts）、雌二醇（E₂）水平,评估计算入组对象的Gensini积分以及LVEF,对比不同组别之间Ts、E₂、Gensini积分以及LVEF差异,Spearman相关分析探究Ts、E₂与Gensini积分、LVEF的相关性,最后将患者按照Genisini评分区分为狭窄轻型组与严重组,Logistic回归分析影响冠脉狭窄的危险因素。结果：（1）比较显示,冠心病各组间Ts、E₂、Gensini积分以及LVEF差异明显,以AMI组患者Ts、E₂和LVEF水平最低,Gensini积分最高（P<0.05）;（2）Spearman相关性分析显示,Ts、E₂均与Gensini积分呈负相关,与LVEF呈正相关（P<0.05）;（3）多因素Logistic回归分析显示Ts、E₂水平是影响冠脉狭窄程度的独立危险因素（P<0.05）。结论：男性内源性性激素水平同其冠心病范围和LVEF呈现密切相关性,是影响冠脉狭窄程度的独立危险因素,可以考虑将其应用于临床冠脉狭窄的诊断与鉴别中。     

Dietary Vitamin D3 Restriction Exacerbates Disease Pathophysiology in the Spinal Cord of the G93A Mouse Model of Amyotrophic Lateral Sclerosis

BackgroundDietary vitamin D₃ (D₃) restriction reduces paw grip endurance and motor performance in G93A mice, and increases inflammation and apoptosis in the quadríceps of females. ALS, a neuromuscular disease, causes progressive degeneration of motor neurons in the brain and spinal cord.ObjectiveWe analyzed the spinal cords of G93A mice following dietary D₃ restriction at 2.5% the adequate intake (AI) for oxidative damage (4-HNE, 3-NY), antioxidant enzymes (SOD2, catalase, GPx1), inflammation (TNF-α, IL-6, IL-10), apoptosis (bax/bcl-2 ratio, cleaved/pro-caspase 3 ratio), neurotrophic factor (GDNF) and neuron count (ChAT, SMI-36/SMI-32 ratio).MethodsBeginning at age 25 d, 42 G93A mice were provided food ad libitum with either adequate (AI;1 IU D₃/g feed; 12 M, 11 F) or deficient (DEF; 0.025 IU D₃/g feed; 10 M, 9 F) D₃. At age 113 d, the spinal cords were analyzed for protein content. Differences were considered significant at P ≤ 0.10, since this was a pilot study.ResultsDEF mice had 16% higher 4-HNE (P = 0.056), 12% higher GPx1 (P = 0.057) and 23% higher Bax/Bcl2 ratio (P = 0.076) vs. AI. DEF females had 29% higher GPx1 (P = 0.001) and 22% higher IL-6 (P = 0.077) vs. AI females. DEF males had 23% higher 4-HNE (P = 0.066) and 18% lower SOD2 (P = 0.034) vs. AI males. DEF males had 27% lower SOD2 (P = 0.004), 17% lower GPx1 (P = 0.070), 29% lower IL-6 (P = 0.023) and 22% lower ChAT (P = 0.082) vs. DEF females.ConclusionD₃ deficiency exacerbates disease pathophysiology in the spinal cord of G93A mice, the exact mechanisms are sex-specific. This is in accord with our previous results in the quadriceps, as well as functional and disease outcomes.