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Whole brain neuroanatomy using tera‐voxel light‐microscopic data sets is of much current interest. A fundamental problem in this field is the mapping of individual brain data sets to a reference space. Previous work has not rigorously quantified in‐vivo to ex‐vivo distortions in brain geometry from tissue processing. Further, existing approaches focus on registering unimodal volumetric data; however, given the increasing interest in the marmoset model for neuroscience research and the importance of addressing individual brain architecture variations, new algorithms are necessary to cross‐register multimodal data sets including MRIs and multiple histological series. Here we present a computational approach for same‐subject multimodal MRI‐guided reconstruction of a series of consecutive histological sections, jointly with diffeomorphic mapping to a reference atlas. We quantify the scale change during different stages of brain histological processing using the Jacobian determinant of the diffeomorphic transformations involved. By mapping the final image stacks to the ex‐vivo post‐fixation MRI, we show that (a) tape‐transfer assisted histological sections can be reassembled accurately into 3D volumes with a local scale change of 2.0 ± 0.4% per axis dimension; in contrast, (b) tissue perfusion/fixation as assessed by mapping the in‐vivo MRIs to the ex‐vivo post fixation MRIs shows a larger median absolute scale change of 6.9 ± 2.1% per axis dimension. This is the first systematic quantification of local metric distortions associated with whole‐brain histological processing, and we expect that the results will generalize to other species. These local scale changes will be important for computing local properties to create reference brain maps. [ABSTRACT FROM AUTHOR]

The degree of intervertebral disc (IVD) degeneration is qualitatively evaluated on T2‐weighted imaging (T2WI). However, it is difficult to assess subtle changes in IVD degeneration using T2WI. Q‐space imaging (QSI) is a quantitative diffusion‐weighted imaging modality used to detect subtle changes in microenvironments. This study aimed to evaluate whether QSI can detect the inhibitory effects of the antioxidant N‐acetylcysteine (NAC) in IVD degeneration. We classified female Wistar rats into control, puncture, and NAC groups (n = 5 per group). In the puncture and NAC groups, IVDs were punctured using a needle. The antioxidant NAC, which suppresses the progression of IVD degeneration, was orally administered in the NAC group 1 week prior to puncture. The progression and inhibitory effect of NAC in IVD degeneration were assessed using magnetic resonance imaging (MRI): IVD height, T2 mapping, apparent diffusion coefficient (ADC), and QSI. MRI was performed using a 7‐Tesla system with a conventional probe (20 IVDs in each group). QSI parameters that were assessed included Kurtosis, the probability at zero displacement (ZDP), and full width at half maximum (FWHM). IVD degeneration by puncture was confirmed by histology, IVD height, T2 mapping, ADC, and all QSI parameters (P <.001); however, the inhibitory effect of NAC was confirmed only by QSI parameters (Kurtosis and ZDP: both P <.001; FWHM: P <.01). Kurtosis had the largest effect size (Kurtosis: 1.13, ZDP: 1.06, and FWHM: 1.02) when puncture and NAC groups were compared. QSI has a higher sensitivity than conventional quantitative methods for detecting the progressive change and inhibitory effect of NAC in IVD degeneration. [ABSTRACT FROM AUTHOR]

Traditionally, the dorsal lateral geniculate nucleus (LGN) and the inferior pulvinar (IPul) nucleus are considered as anatomically and functionally distinct thalamic nuclei. However, in several primate species it has also been established that the koniocellular (K) layers of LGN and parts of the IPul have a shared pattern of immunoreactivity for the calcium‐binding protein calbindin. These calbindin‐rich cells constitute a thalamic matrix system which is implicated in thalamocortical synchronisation. Further, the K layers and IPul are both involved in visual processing and have similar connections with retina and superior colliculus. Here, we confirmed the continuity between calbindin‐rich cells in LGN K layers and the central lateral division of IPul (IPulCL) in marmoset monkeys. By employing a high‐throughput neuronal tracing method, we found that both the K layers and IPulCL form comparable patterns of connections with striate and extrastriate cortices; these connections are largely different to those of the parvocellular and magnocellular laminae of LGN. Retrograde tracer‐labelled cells and anterograde tracer‐labelled axon terminals merged seamlessly from IPulCL into LGN K layers. These results support continuity between LGN K layers and IPulCL, providing an anatomical basis for functional congruity of this region of the dorsal thalamic matrix and calling into question the traditional segregation between LGN and the inferior pulvinar nucleus. [ABSTRACT FROM AUTHOR]

Background: Precise imaging of nerves have been challenging in the head and neck region, mainly due to low spatial resolution. Here, we investigated how nerves in the head and neck region could be visualized using an ultra‐high magnetic field MR system. Methods: We used formol‐carbol‐fixed human cadaveric necks and obtained MR diffusion tensor images (DTIs) using a 9.4 Tesla (T) ultra‐high magnetic field MR system. Afterward, we prepared tissue sections and checked the anatomic relationships between the neurons and the carotid artery in order to confirm that the visualized fibers are indeed neuron fibers. Results: We were able to identify nerves, including the vagus nerve, the hypoglossal nerve, and the spinal‐accessory nerve. Hematoxylin‐eosin stained histological sections confirmed neuron fibers in the same anatomic position. Conclusion: This technique has the feasibility to be applied for a more accurate anatomic understanding, maybe even close to a histological level. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the use of non-Gaussian diffusion-weighted imaging (q-space imaging [QSI]) to estimate diurnal changes in intervertebral disc (IVD) microstructure. Materials and Methods: IVDs of 15 male subjects (mean age, 27.3 years; mean body mass index, 22.50 kg/ m2) were investigated once in the morning, less than 30 min after rising, and a second time in the evening after at least 10 h of normal physical activity, using 3 Tesla (T) MR imaging. T2 mapping and QSI data values (apparent diffusion coefficient [ADC], root mean square displacement [RMSD], and apparent kurtosis coefficient [AKC]) were calculated and compared between the morning and evening imaging sessions. Results: The T2, ADC, and RMSD values showed a significant decrease in the evening (175.8 ±49.5 ms, 1.56±0.32 10-3mm2/s and 40.0 ± 3.0 μm, respectively; P<0.05 for all values; paired t-test), when compared with the morning values (226.5± 83.8 ms, 1.69 ± 0.29 10-3mm2/s and 45.2±2.9 μm, respectively). The AKC value showed a significant increase in the evening (0.67±0.08), when compared with the morning value (0.58± 0.04; P<0.05). Conclusion: The RMSD and AKC values obtained from QSI analysis may be biomarkers for IVD diurnal microstructural changes. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma is the most common soft tissue sarcoma affecting children, and the overall cure rate of children with metastatic disease remains below 30%. The CXC chemokine receptor-4 ( CXCR4)/stromal cell-derived factor-1 ( SDF1) axis has been implicated in the promotion of metastatic potential in several tumors. In this study, we developed a novel anti- CXCR4 m Ab, CF172, and investigated its antimetastatic activity against rhabdomyosarcoma cells in vitro and in vivo, to evaluate its potential as a therapeutic antibody to treat rhabdomyosarcoma. The CF172 molecule showed a specific binding reactivity against human CXCR4, as well as a specific neutralizing activity against CXCR4/ SDF1 signal transduction. Using CF172, we determined that SJCRH30 rhabdomyosarcoma cells expressed high levels of CXCR4. In addition, CF172 was found to inhibit the SDF1-induced migration activity of SJCRH30 cells in vitro. Using xenograft models of SJCRH30 cells, we carried out in vivo efficacy studies for peritoneal and lymph node metastasis, which were clinically observed in rhabdomyosarcoma. These studies indicated that CF172 significantly decreased both types of metastasis of SJCRH30. In conclusion, we found that a novel anti- CXCR4 m Ab, CF172, with specific reactivity against human CXCR4, prevented peritoneal metastasis and lymph node metastasis of rhabdomyosarcoma in animal models. These results suggest that CF172 is a potential antimetastasis therapeutic antibody for rhabdomyosarcoma treatment. [ABSTRACT FROM AUTHOR]

Lymphatic spread is an important clinical determinant in the prognosis of many human cancers. The lymphangiogenic factor vascular endothelial growth factor- D ( VEGF-D) is implicated in the promotion of lymphatic metastasis through the development of lymphatic vessels in some human cancers. In this study, we developed an anti- VEGF-D monoclonal antibody, cVE199, and investigated its in vitro properties, in vivo effects against tumors and possible target indications to evaluate its potential as a therapeutic antibody. The cVE199 molecule was revealed to have a specific binding reactivity against human VEGF-D, as well as a specific inhibitory activity against the binding of human VEGF-D to VEGFR-3. In addition, cVE199 was found to inhibit the biological activity of VEGF-D against lymphatic cells in vitro. Because we determined that a neuroblastoma cell line, SK-N-DZ, abundantly expressed VEGF-D, an in vivo efficacy study was performed using a xenograft model of SK-N-DZ. We found that cVE199 significantly decreased lymphatic metastasis of SK-N-DZ as well as lymphangiogenesis in primary lesions. Finally, we investigated VEGF-D expression in human neuroblastoma, finding that the molecule was expressed in 11 of 29 human neuroblastoma specimens (37.9%). In conclusion, we found that a novel anti- VEGF-D monoclonal antibody, cVE199, with specific reactivity against human VEGF-D, prevents lymphatic metastasis of neuroblastoma through the inhibition of lymphangiogenesis in an animal model. In addition, our results show that VEGF-D is expressed in some cases of human neuroblastomas, which suggests that cVE199 is a potential anti-metastasis therapeutic antibody in neuroblastoma treatment. [ABSTRACT FROM AUTHOR]