Gray Matter Of Cervical Spinal Cord Research Articles

Effects of Photon versus Carbon-Ion Irradiation in the Rat Cervical Spinal Cord - a Serial T2 and Diffusion-weighted Magnetic Resonance Imaging Study.

Carbon-ion irradiation is increasingly used at the skull base and spine near the radiation-sensitive spinal cord. To better characterize the invivo radiation response of the cervical spinal cord, radiogenic changes in the high-dose area were measured in rats using magnetic resonance imaging (MRI) diffusion measurements in comparison to conventional photon irradiations. In this longitudinal MRI study, we examined the gray matter (GM) of the cervical spinal cord in 16 female Sprague-Dawley rats after high-dose photon (n = 8) or carbon-ion (12C) irradiation (n = 8) and in 6 sham-exposed rats until myelopathy occurred. The differences in the diffusion pattern of the GM of the cervical spinal cord were examined until the endpoint of the study, occurrence of paresis grade II of both forelimbs was reached. In both radiation techniques, the same order of the occurrence of MR-morphological pathologies was observed - from edema formation to a blood spinal cord barrier (BSCB) disruption to paresis grade II of both forelimbs. However, carbon-ion irradiation showed a significant increase of the mean apparent diffusion coefficient (ADC; P = 0.031) with development of a BSCB disruption in the GM. Animals with paresis grade II as a late radiation response had a highly significant increase in mean ADC (P = 0.0001) after carbon-ion irradiation. At this time, a tendency was observed for higher mean ADC values in the GM after 12C irradiation as compared to photon irradiation (P = 0.059). These findings demonstrated that carbon-ion irradiation leads to greater structural damage to the GM of the rat cervical spinal cord than photon irradiation due to its higher linear energy transfer (LET) value.

Cervical Spinal Cord Gray Matter Atrophy as an Emerging Imaging Marker in Spinal Muscular Atrophy (P2-8.014)

<h3>Objective:</h3> To prospectively evaluate cervical spinal cord (SC) gray matter (GM) area and its association with upper limb function in patients with 5q-Spinal Muscular Atrophy (SMA) using rAMIRA (radially sampled Magnetization Inversion Recovery Acquisitions) MR-imaging. <h3>Background:</h3> With the approval of the first disease modifying treatments for SMA, there is an increasing need for biomarkers that allow easy to perform, reliable, and valid disease course- and therapeutic response monitoring. The novel rAMIRA method enables high in-plane resolution MR-imaging with improved contrast of SC GM in clinically feasible acquisition times at 3 Tesla. <h3>Design/Methods:</h3> Using axial 2D rAMIRA imaging, we prospectively investigated 21 patients with 5q-SMA, types 2 and 3 (mean age/SD 41.3/11.6y, 9 women) and 21 age- and sex-matched healthy controls (HC) (mean age/SD 41.7/11.4y, 9 women) at the intervertebral disc levels C2/C3-C5/C6 perpendicular to the cord. SC GM areas were determined using a semi-automated approach. The associations between SC GM area and Revised Upper Limb Module (RULM), an established measure of upper limb disability in SMA, were assessed using multivariable regression analysis covarying for age. <h3>Results:</h3> Compared to HC cervical SC GM areas were significantly reduced in patients with SMA at C3/C4 with a relative reduction (RR) of 13.6% (p&lt;0.0001), at C4/5 RR = 16.7%, (p&lt;0.0001), at C5/6 RR = 17.1% (p&lt;0.0001), but not significantly at C2/C3 RR = 5.3% (p=0.071). In multivariable regression analysis covarying for age, GM area at C3/C4 explained 28% of RULM variance in patients with SMA. <h3>Conclusions:</h3> Cervical SC GM atrophy is detectable in patients with 5q SMA compared to HC and correlates with clinical measures of upper limb function, namely RULM. Further longitudinal investigations are necessary next steps to evaluate the potential of this novel and easy to assess imaging marker for monitoring the disease course and therapeutic response. <b>Disclosure:</b> Dr. Kesenheimer has nothing to disclose. Dr. Wendebourg has nothing to disclose. An immediate family member of Dr. Weidensteiner has received personal compensation for serving as an employee of Siemens Healthineers. Dr. Sander has nothing to disclose. The institution of Matthias Weigel, PhD has received research support from Biogen. Matthias Weigel, PhD has received intellectual property interests from a discovery or technology relating to health care. Tanja Haas has nothing to disclose. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann La Roche AG. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann La Roche AG. Christoph Neuwirth has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen USA. Christoph Neuwirth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Switzerland. Nathalie Braun has nothing to disclose. Dr. Weber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Weber has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Granziera has nothing to disclose. Prof. Sinnreich has nothing to disclose. The institution of Oliver Bieri has received research support from Swiss National Science Foundation. The institution of Oliver Bieri has received research support from MIAC Foundation. The institution of Oliver Bieri has received research support from Biogen. Oliver Bieri has received intellectual property interests from a discovery or technology relating to health care. Regina Schlaeger has nothing to disclose.

Cervical Spinal Cord Gray Matter Area is Associated with Motor Unit Number Index in Spinal Muscular Atrophy (S33.008)

<h3>Objective:</h3> To evaluate the association between spinal cord (SC) gray matter (GM) atrophy and Motor Unit Number Index (MUNIX) in patients with 5q-Spinal Muscular Atrophy (SMA). <h3>Background:</h3> There is an unmet need for valid imaging markers to monitor the disease course and therapeutic outcome in SMA. The novel rAMIRA (radially sampled Averaged Magnetization Inversion Recovery Acquisitions) method enables high in-plane resolution MR-imaging with improved contrast of SC GM in clinically feasible acquisition times. MUNIX is an established quantitative neurophysiological measure that provides an index of the number of functioning lower motor neurons that supply a muscle. The association between SC GM area and MUNIX has not been investigated in SMA yet. <h3>Design/Methods:</h3> Using axial 2D rAMIRA imaging, we prospectively investigated 21 patients with 5q-SMA, types 2 and 3 (mean age/SD 41.3/11.6y, 9 women) and 21 age- and sex-matched healthy controls (HC) (mean age/SD 41.7/11.4y, 9 women) at the intervertebral disc level C5/C6 perpendicular to the spinal cord. SC GM areas were determined using a semi-automated approach. MUNIX of the biceps brachii (BB) was measured following the ENCALS protocol. The association between SC GM area and MUNIX was assessed using multivariable regression analysis covarying for age and sex. <h3>Results:</h3> SC GM area at C5/6 was significantly reduced in patients compared to HC (mean GM area in mm² (SD): SMA 17.5 (2.2); HC 21.1 (2.3); relative reduction: 17.1% (p&lt;0.0001)). In multivariable regression analysis SC GM area at C5/6 explained 53% of MUNIX variance of the BB in SMA patients. <h3>Conclusions:</h3> In patients with SMA, SC GM area is strongly associated with motor neuron function quantitated by MUNIX in the corresponding myotome, indicating the functional relevance of this structural marker. Further longitudinal studies are necessary to evaluate the potential of this novel imaging marker for monitoring the disease course and therapeutic outcome. <b>Disclosure:</b> Dr. Wendebourg has nothing to disclose. Dr. Kesenheimer has nothing to disclose. An immediate family member of Dr. Weidensteiner has received personal compensation for serving as an employee of Siemens Healthineers. Dr. Sander has nothing to disclose. The institution of Matthias Weigel, PhD has received research support from Biogen. Matthias Weigel, PhD has received intellectual property interests from a discovery or technology relating to health care. Tanja Haas has nothing to disclose. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann La Roche AG. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann La Roche AG. Christoph Neuwirth has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen USA. Christoph Neuwirth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Switzerland. Nathalie Braun has nothing to disclose. Dr. Weber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Weber has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Granziera has nothing to disclose. Prof. Sinnreich has nothing to disclose. The institution of Oliver Bieri has received research support from Swiss National Science Foundation. The institution of Oliver Bieri has received research support from MIAC Foundation. The institution of Oliver Bieri has received research support from Biogen. Oliver Bieri has received intellectual property interests from a discovery or technology relating to health care. Regina Schlaeger has nothing to disclose.

Measurement of T2* in the human spinal cord at 3T.

To measure the transverse relaxation time T2* in healthy human cervical spinal cord gray matter (GM) and white matter (WM) at 3T. Thirty healthy volunteers were recruited. Axial images were acquired using an averaged multi-echo gradient-echo (mFFE) T2*-weighted sequence with 5 echoes. We used the signal equation for an mFFE sequence with constant dephasing gradients after each echo to jointly estimate the spin density and T2* for each voxel. No global difference in T2* was observed between all GM (41.3 ± 5.6ms) and all WM (39.8 ± 5.4ms). No significant differences were observed between left (43.2 ± 6.8ms) and right (43.4 ± 5.5ms) ventral GM, left (38.3 ± 6.1ms) and right (38.6 ± 6.5ms) dorsal GM, and left (39.4 ± 5.8ms) and right (40.3 ± 5.8ms) lateral WM. However, significant regional differences were observed between ventral (43.4 ± 5.7ms) and dorsal (38.4 ± 6.0ms) GM (p<0.05), as well as between ventral (42.9 ± 6.5ms) and dorsal (37.9 ± 6.2ms) WM (p<0.05). In analyses across slices, inferior T2* was longer than superior T2* in GM (44.7ms vs. 40.1ms; p<0.01) and in WM (41.8ms vs. 35.9ms; p<0.01). Significant differences in T2* are observed between ventral and dorsal GM, ventral and dorsal WM, and superior and inferior GM and WM. There is no evidence for bilateral asymmetry in T2* in the healthy cord. These values of T2* in the spinal cord are notably lower than most reported values of T2* in the cortex.

Directional regrowth of lesioned corticospinal tract axons in adult rat spinal cord.

During central nervous system development, gradients of diffusible molecules play an important role in the attraction of outgrowing axons. A diffusible tropic factor released by the cervical spinal gray matter attracts outgrowing corticospinal tract axons, as shown by in vitro collagen co-culture studies [Joosten E. A. J. et al. (1994) Neuroscience 59, 33-41]. Here we study the effects of local application of timed cervical spinal gray matter extracts on regrowth of injured corticospinal tract axons in the adult rat spinal cord. For local application of target-derived extracts at the site of lesion we used rat tail collagen type 1 as a matrix. Ingrowth of anterogradely labelled corticospinal tract axons into the collagen was studied four weeks after the spinal cord injury. No ingrowth of labelled corticospinal tract axons can be observed in the control experiment when collagen only was applied into the lesion gap. Furthermore, we found that local application of an extract derived from four-day, but not from one-day or 16-day-old, cervical spinal cord gray matter directs a substantial amount of the lesioned adult corticospinal tract axons into the collagen implant. We conclude that directional regrowth of injured corticospinal tract axons in the adult rat spinal cord is possible by local application of timed target-derived extracts. In this respect spatiotemporal aspects are of the utmost importance.

Selective elimination of transient corticospinal projections in the rat cervical spinal cord gray matter

In the present paper a description is given of the development of the rat corticospinal tract (CST) in the lower cervical spinal cord. This area contains, among other cells, the motoneurons innervating the distal forelimb muscles. HRP gels were implanted in the sensorimotor cortex of Wistar rats varying in age from postnatal day 0 (P0) to P60. After a survival period of 48 h, the rats were transcardially perfused, the spinal cords transversely sectioned at 30 μm and the sections reacted for HRP. Labelled CST axons in the dorsal funiculus were first detected at P2, and after a delay of 2 days the first fibres were found in the adjacent gray matter (P4). More labelled fibres were gradually added until maximal number and extension was reached at P10. By then the entire gray matter and large parts of the white matter were covered by labelled CST axons. From P10 onwards, the number of labelled CST fibres as well as their extension decreased. In the adult rat, some areas such as the lateral part of the ventral and dorsal horn and large parts of the ventral and lateral white matter ultimately became devoid of labelled CST axons. It is concluded that a massive overshoot occurs during the development of the terminal field of the rat CST. The results are discussed in conjunction with our previous findings on the development of the motoneuron innervating the rat distal forelimb muscles. The concurrent selective elimination of both CST axons and motoneuron dendrites is suggested to be correlated with progressively more mature, coordinated movements and with high digital skills especially.