Bio

Bio


Dr. Leuze is working on techniques for visualization of MRI data using virtual and augmented reality devices. He has developed an MRI viewer for the Samsung Gear VR and has presented projects on MRI data volumetric visualization and registration to the real world using the Microsoft Hololens and the Intel RealSense camera. Dr. Leuze is furthermore refining MRI techniques for measuring brain circuits by validation with tissue clearing and optical imaging methods.

Honors & Awards


  • Stanford Neuroscience Insitute Interdisciplinary Scholar Awards, Stanford Neuroscience Insitute (2015)
  • Otto-Hahn-Medal, Max Planck Society (2014)

Education & Certifications


  • PhD, Max Planck Institute for Human Cognitive and Brain Sciences & University of Leipzig, Physics (2013)
  • MS, University of Leipzig, Physics (2008)

Projects


  • BrainVR (5/2016 - 10/2016)

    VR app about the brain for the Samsung Gear VR

    Location

    Stanford, USA

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  • Ars Electronica (7/2013 - 9/2013)

    Production of a 3D movie about the brain for the Ars Electronica 2013 in Linz/Austria

    Location

    Linz, Austria

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Publications

All Publications


  • Comparison of diffusion MRI and CLARITY fiber orientation estimates in both gray and white matter regions of human and primate brain. NeuroImage Leuze, C., Goubran, M., Barakovic, M., Aswendt, M., Tian, Q., Hsueh, B., Crow, A., Weber, E. M., Steinberg, G. K., Zeineh, M., Plowey, E. D., Daducci, A., Innocenti, G., Thiran, J., Deisseroth, K., McNab, J. A. 2020; 228: 117692

    Abstract

    Diffusion MRI (dMRI) represents one of the few methods for mapping brain fiber orientations non-invasively. Unfortunately, dMRI fiber mapping is an indirect method that relies on inference from measured diffusion patterns. Comparing dMRI results with other modalities is a way to improve the interpretation of dMRI data and help advance dMRI technologies. Here, we present methods for comparing dMRI fiber orientation estimates with optical imaging of fluorescently labeled neurofilaments and vasculature in 3D human and primate brain tissue cuboids cleared using CLARITY. The recent advancements in tissue clearing provide a new opportunity to histologically map fibers projecting in 3D, which represents a captivating complement to dMRI measurements. In this work, we demonstrate the capability to directly compare dMRI and CLARITY in the same human brain tissue and assess multiple approaches for extracting fiber orientation estimates from CLARITY data. We estimate the three-dimensional neuronal fiber and vasculature orientations from neurofilament and vasculature stained CLARITY images by calculating the tertiary eigenvector of structure tensors. We then extend CLARITY orientation estimates to an orientation distribution function (ODF) formalism by summing multiple sub-voxel structure tensor orientation estimates. In a sample containing part of the human thalamus, there is a mean angular difference of 19o±15o between the primary eigenvectors of the dMRI tensors and the tertiary eigenvectors from the CLARITY neurofilament stain. We also demonstrate evidence that vascular compartments do not affect the dMRI orientation estimates by showing an apparent lack of correspondence (mean angular difference=49o±23o) between the orientation of the dMRI tensors and the structure tensors in the vasculature stained CLARITY images. In a macaque brain dataset, we examine how the CLARITY feature extraction depends on the chosen feature extraction parameters. By varying the volume of tissue over which the structure tensor estimates are derived, we show that orientation estimates are noisier with more spurious ODF peaks for sub-voxels below 30m3 and that, for our data, the optimal gray matter sub-voxel size is between 62.5m3 and 125m3. The example experiments presented here represent an important advancement towards robust multi-modal MRI-CLARITY comparisons.

    View details for DOI 10.1016/j.neuroimage.2020.117692

    View details for PubMedID 33385546

  • Comparison of head pose tracking methods for mixed-reality neuronavigation for transcranial magnetic stimulation SPIE Medical Imaging Sathyanarayana, S., Leuze, C., Hargreaves, B., Daniel, B. L., Wetzstein, G., Etkin, A., Bhati, M. T., McNab, J. A. 2020

    View details for DOI 10.1117/12.2547917

  • Landmark-based mixed-reality perceptual alignment of medical imaging data and accuracy validation in living subjects IEEE International Symposium on Mixed and Augmented Reality (ISMAR) Leuze, C., Sathyanarayana, S., Daniel, B. L., McNab, J. A. 2020
  • Application of holographic augmented reality for external approaches to the frontal sinus. International forum of allergy & rhinology Neves, C. A., Vaisbuch, Y., Leuze, C., McNab, J. A., Daniel, B., Blevins, N. H., Hwang, P. H. 2020

    Abstract

    External approaches to the frontal sinus such as osteoplastic flaps are challenging because they require blind entry into the sinus, posing risks of injury to the brain or orbit. Intraoperative computed tomography (CT)-based navigation is the current standard for planning the approach, but still necessitates blind entry into the sinus. The aim of this work was to describe a novel technique for external approaches to the frontal sinus using a holographic augmented reality (AR) application.Our team developed an AR system to create a 3-dimensional (3D) hologram of key anatomical structures, based on CT scans images. Using Magic Leap AR goggles for visualization, the frontal sinus hologram was aligned to the surface anatomy in 6 fresh cadaveric heads' anatomic boundaries, and the boundaries of the frontal sinus were demarcated based on the margins of the fused image. Trephinations and osteoplastic flap approaches were performed. The specimens were re-scanned to assess the accuracy of the osteotomy with respect to the actual frontal sinus perimeter.Registration and surgery were completed successfully in all specimens. Registration required an average of 2 minutes. The postprocedure CT showed a mean difference of 1.4 ± 4.1 mm between the contour of the osteotomy and the contour of the frontal sinus. One surgical complication (posterior table perforation) occurred (16%).We describe proof of concept of a novel technique utilizing AR to enhance external approaches to the frontal sinus. Holographic AR-enhanced surgical navigation holds promise for enhanced visualization of target structures during surgical approaches to the sinuses.

    View details for DOI 10.1002/alr.22546

    View details for PubMedID 32362076

  • Multimodal characterization of the human nucleus accumbens NEUROIMAGE Cartmell, S. D., Tian, Q., Thio, B. J., Leuze, C., Ye, L., Williams, N. R., Yang, G., Ben-Dor, G., Deisseroth, K., Grill, W. M., McNab, J. A., Halpern, C. H. 2019; 198: 137?49
  • Generalized diffusion spectrum magnetic resonance imaging (GDSI) for model-free reconstruction of the ensemble average propagator NEUROIMAGE Tian, Q., Yang, G., Leuze, C., Rokem, A., Edlow, B. L., McNab, J. A. 2019; 189: 497?515
  • Multimodal image registration and connectivity analysis for integration of connectomic data from microscopy to MRI. Nature communications Goubran, M., Leuze, C., Hsueh, B., Aswendt, M., Ye, L., Tian, Q., Cheng, M. Y., Crow, A., Steinberg, G. K., McNab, J. A., Deisseroth, K., Zeineh, M. 2019; 10 (1): 5504

    Abstract

    3D histology, slice-based connectivity atlases, and diffusion MRI are common techniques to map brain wiring. While there are many modality-specific tools to process these data, there is a lack of integration across modalities. We develop an automated resource that combines histologically cleared volumes with connectivity atlases and MRI, enabling the analysis of histological features across multiple fiber tracts and networks, and their correlation with in-vivo biomarkers. We apply our pipeline in a murine stroke model, demonstrating not only strong correspondence between MRI abnormalities and CLARITY-tissue staining, but also uncovering acute cellular effects in areas connected to the ischemic core. We provide improved maps of connectivity by quantifying projection terminals from CLARITY viral injections, and integrate diffusion MRI with CLARITY viral tracing to compare connectivity maps across scales. Finally, we demonstrate tract-level histological changes of stroke through this multimodal integration. This resource can propel investigations of network alterations underlying neurological disorders.

    View details for DOI 10.1038/s41467-019-13374-0

    View details for PubMedID 31796741

  • RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke STROKE Ito, M., Aswendt, M., Lee, A. G., Ishizaka, S., Cao, Z., Wang, E. H., Levy, S. L., Smerin, D. L., McNab, J. A., Zeineh, M., Leuze, C., Goubran, M., Cheng, M. Y., Steinberg, G. K. 2018; 49 (9): 2191?99
  • Double diffusion encoding MRI for the clinic MAGNETIC RESONANCE IN MEDICINE Yang, G., Tian, Q., Leuze, C., Wintermark, M., McNab, J. A. 2018; 80 (2): 507?20

    Abstract

    The purpose of this study is to develop double diffusion encoding (DDE) MRI methods for clinical use. Microscopic diffusion anisotropy measurements from DDE promise greater specificity to changes in tissue microstructure compared with conventional diffusion tensor imaging, but implementation of DDE sequences on whole-body MRI scanners is challenging because of the limited gradient strengths and lengthy acquisition times.A custom single-refocused DDE sequence was implemented on a 3T whole-body scanner. The DDE gradient orientation scheme and sequence parameters were optimized based on a Gaussian diffusion assumption. Using an optimized 5-min DDE acquisition, microscopic fractional anisotropy (?FA) maps were acquired for the first time in multiple sclerosis patients.Based on simulations and in vivo human measurements, six parallel and six orthogonal diffusion gradient pairs were found to be the minimum number of diffusion gradient pairs necessary to produce a rotationally invariant measurement of ?FA. Simulations showed that optimal precision and accuracy of ?FA measurements were obtained using b-values between 1500 and 3000 s/mm2 . The ?FA maps showed improved delineation of multiple sclerosis lesions compared with conventional fractional anisotropy and distinct contrast from T2 -weighted fluid attenuated inversion recovery and T1 -weighted imaging.The ?FA maps can be measured using DDE in a clinical setting and may provide new opportunities for characterizing multiple sclerosis lesions and other types of tissue degeneration. Magn Reson Med 80:507-520, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

    View details for PubMedID 29266375

    View details for PubMedCentralID PMC5910247

  • Marker-less co-registration of MRI data to a subject?s head via a mixed reality device 26th Annual meeting of the International Society for Magnetic Resonance in Medicine Leuze, C., Yang, G., Wetzstein, G., Mahendra, B., Etkin, A., McNab, J. 2018
  • Mixed-reality guidance for brain stimulation treatment of depression Leuze, C., Yang, G., Hargreaves, B., Daniel, B., Mcnab, J. A., IEEE IEEE. 2018: 377?80
  • The separate effects of lipids and proteins on brain MRI contrast revealed through tissue clearing. NeuroImage Leuze, C., Aswendt, M., Ferenczi, E., Liu, C. W., Hsueh, B., Goubran, M., Tian, Q., Steinberg, G., Zeineh, M. M., Deisseroth, K., McNab, J. A. 2017

    Abstract

    Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the relative contribution of different biological components (e.g. lipids and proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density, diffusion) remains incompletely understood. This limitation can undermine the interpretation of clinical MRI and hinder the development of new contrast mechanisms. Here, we determine the respective contribution of lipids and proteins to MRI contrast by removing lipids and preserving proteins in mouse brains using CLARITY. We monitor the temporal dynamics of tissue clearance via NMR spectroscopy, protein assays and optical emission spectroscopy. MRI of cleared brain tissue showed: 1) minimal contrast on standard MRI sequences; 2) increased relaxation times; and 3) diffusion rates close to free water. We conclude that lipids, present in myelin and membranes, are a dominant source of MRI contrast in brain tissue.

    View details for DOI 10.1016/j.neuroimage.2017.04.021

    View details for PubMedID 28411157

  • Holographic Visualization of Brain MRI with Real-Time Alignment to a Human Subject 25th Annual meeting of the International Society for Magnetic Resonance in Medicine Leuze, C., Subashini, S., Lin, M., Hargreaves, B., Daniel, B., McNab, J. 2017
  • The separate effects of lipids and proteins on brain MRI contrast revealed through tissue clearing. NeuroImage Leuze, C., Aswendt, M., Ferenczi, E., Liu, C. W., Hsueh, B., Goubran, M., Tian, Q., Steinberg, G., Zeineh, M. M., Deisseroth, K., McNab, J. A. 2017

    Abstract

    Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the relative contribution of different biological components (e.g. lipids and proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density, diffusion) remains incompletely understood. This limitation can undermine the interpretation of clinical MRI and hinder the development of new contrast mechanisms. Here, we determine the respective contribution of lipids and proteins to MRI contrast by removing lipids and preserving proteins in mouse brains using CLARITY. We monitor the temporal dynamics of tissue clearance via NMR spectroscopy, protein assays and optical emission spectroscopy. MRI of cleared brain tissue showed: 1) minimal contrast on standard MRI sequences; 2) increased relaxation times; and 3) diffusion rates close to free water. We conclude that lipids, present in myelin and membranes, are a dominant source of MRI contrast in brain tissue.

    View details for PubMedID 28411157

  • Early Non-invasive Detection of Acute 1,2-Dichloroethane-induced Toxic Encephalopathy in Rats. In vivo Zhou, X., Cao, Y., Leuze, C., Nie, B., Shan, B., Zhou, W., Cipriano, P., Xiao, B. O. 2016; 30 (6): 787-793

    Abstract

    To assess the acute effect of 1,2-dichloroethane (1,2-DCE) on rat brain using diffusion magnetic resonance imaging (dMRI).We performed dMRI on 30 male Sprague-Dawley rats, microstructural alterations were investigated by calculating the mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) changes in eight selected brain regions of interest. For the whole brain, clusters of 20+ voxels that differed significantly in FA and ADC between groups were marked. Hematoxylin-eosin staining was performed to confirm pathological changes.Brain images showed lesions with brain edema in the white matter in both hemispheres in all groups exposed to 1,2-DCE. Diffusivity values were significantly different after 1,2-DCE inhalation (p<0.05).Primarily cytotoxic edema occurred in acute 1,2-DCE-induced brain edema in rats. dMRI could be used for the early non-invasive detection of acute 1,2-DCE-induced toxic encephalopathy.

    View details for PubMedID 27815462

  • Layer-Specific Intracortical Connectivity Revealed with Diffusion MRI CEREBRAL CORTEX Leuze, C. W., Anwander, A., Bazin, P., Dhital, B., Stueber, C., Reimann, K., Geyer, S., Turner, R. 2014; 24 (2): 328-339

    Abstract

    In this work, we show for the first time that the tangential diffusion component is orientationally coherent at the human cortical surface. Using diffusion magnetic resonance imaging (dMRI), we have succeeded in tracking intracortical fiber pathways running tangentially within the cortex. In contrast with histological methods, which reveal little regarding 3-dimensional organization in the human brain, dMRI delivers additional understanding of the layer dependence of the fiber orientation. A postmortem brain block was measured at very high angular and spatial resolution. The dMRI data had adequate resolution to allow analysis of the fiber orientation within 4 notional cortical laminae. We distinguished a lamina at the cortical surface where diffusion was tangential along the surface, a lamina below the surface where diffusion was mainly radial, an internal lamina covering the Stria of Gennari, where both strong radial and tangential diffusion could be observed, and a deep lamina near the white matter, which also showed mainly radial diffusion with a few tangential compartments. The measurement of the organization of the tangential diffusion component revealed a strong orientational coherence at the cortical surface.

    View details for DOI 10.1093/cercor/bhs311

    View details for Web of Science ID 000329840900005

    View details for PubMedID 23099298

  • Myelin and iron concentration in the human brain: A quantitative study of MRI contrast. NeuroImage Stüber, C., Morawski, M., Schäfer, A., Labadie, C., Wähnert, M., Leuze, C., Streicher, M., Barapatre, N., Reimann, K., Geyer, S., Spemann, D., Turner, R. 2014

    Abstract

    During the last five years ultra-high-field magnetic resonance imaging (MRI) has enabled an unprecedented view of living human brain. Brain tissue contrast in most MRI sequences is known to reflect mainly the spatial distributions of myelin and iron. These distributions have been shown to overlap significantly in many brain regions, especially in the cortex. It is of increasing interest to distinguish and identify cortical areas by their appearance in MRI, which has been shown to be feasible in vivo. Parcellation can benefit greatly from quantification of the independent contributions of iron and myelin to MRI contrast. Recent studies using susceptibility mapping claim to allow such a separation of the effects of myelin and iron in MRI. We show, using post-mortem human brain tissue, that this goal can be achieved. After MRI scanning of the block with appropriate T1 mapping and T2* weighted sequences, we section the block and apply a novel technique, proton induced X-ray emission (PIXE), to spatially map iron, phosphorus and sulfur elemental concentrations, simultaneously with 1?m spatial resolution. Because most brain phosphorus is located in myelin phospholipids, a calibration step utilizing element maps of sulfur enables semi-quantitative ex vivo mapping of myelin concentration. Combining results for iron and myelin concentration in a linear model, we have accurately modeled MRI tissue contrasts. Conversely, iron and myelin concentrations can now be estimated from appropriate MRI measurements in post-mortem brain samples.

    View details for DOI 10.1016/j.neuroimage.2014.02.026

    View details for PubMedID 24607447

  • Systematic changes to the apparent diffusion tensor of in vivo rat brain measured with an oscillating-gradient spin-echo sequence NEUROIMAGE Kershaw, J., Leuze, C., Aoki, I., Obata, T., Kanno, I., Ito, H., Yamaguchi, Y., Handa, H. 2013; 70: 10-20

    Abstract

    As the oscillating gradient spin-echo sequence has shown promise as a means to probe tissue microstructure, it was applied here to diffusion-tensor imaging of in vivo rat brain. The apparent diffusion tensor (ADT) was estimated for motion-probing gradient (MPG) frequencies in the range 33.3-133.3 Hz, and regions-of-interest (ROIs) in the corpus callosum (CC), visual cortex (VC), cerebellar white matter (CBWM) and cerebellar grey matter (CBGM) were selected for detailed analysis. There were substantial, approximately linear changes to the ADT with increasing MPG frequency for all four ROIs. All ROIs showed clear increases in mean diffusivity. CBWM had a substantial decrease in fractional anisotropy, whereas the CC and VC had minor increases of the same parameter. All eigenvalues of the ADT tended to increase with frequency for the CBWM, CBGM and VC, but only the principal eigenvalue increased strongly for the CC. On the other hand, there was no evidence that the orientation of the principal eigenvector varied systematically with MPG frequency for any of the ROIs. The relationship between the behaviour of the eigenvalues and the behaviours of the mean diffusivity and fractional anisotropy is investigated in detail. Pixelwise linear fits to the MD from individual animals found elevated changes across the cerebellum. The data acquired for this work encompassed a range of effective diffusion-times from 7.5 ms down to 1.875 ms, and some ideas on how the results might be used to extract quantitative information about brain tissue microstructure are discussed.

    View details for DOI 10.1016/j.neuroimage.2012.12.036

    View details for Web of Science ID 000315703800002

    View details for PubMedID 23274188

  • Quantitative measurement of changes in calcium channel activity in vivo utilizing dynamic manganese-enhanced MRI (dMEMRI) NEUROIMAGE Leuze, C., Kimura, Y., Kershaw, J., Shibata, S., Saga, T., Chuang, K., Shimoyama, I., Aoki, I. 2012; 60 (1): 392-399

    Abstract

    The ability of manganese ions (Mn(2+)) to enter cells through calcium ion (Ca(2+)) channels has been used for depolarization dependent brain functional imaging with manganese-enhanced MRI (MEMRI). The purpose of this study was to quantify changes to Mn(2+) uptake in rat brain using a dynamic manganese-enhanced MRI (dMEMRI) scanning protocol with the Patlak and Logan graphical analysis methods. The graphical analysis was based on a three-compartment model describing the tissue and plasma concentration of Mn. Mn(2+) uptake was characterized by the total distribution volume of manganese (Mn) inside tissue (V(T)) and the unidirectional influx constant of Mn(2+) from plasma to tissue (K(i)). The measurements were performed on the anterior (APit) and posterior (PPit) parts of the pituitary gland, a region with an incomplete blood brain barrier. Modulation of Ca(2+) channel activity was performed by administration of the stimulant glutamate and the inhibitor verapamil. It was found that the APit and PPit showed different Mn(2+) uptake characteristics. While the influx of Mn(2+) into the PPit was reversible, Mn(2+) was found to be irreversibly trapped in the APit during the course of the experiment. In the PPit, an increase of Mn(2+) uptake led to an increase in V(T) (from 2.8±0.3 ml/cm(3) to 4.6±1.2 ml/cm(3)) while a decrease of Mn(2+) uptake corresponded to a decrease in V(T) (from 2.8±0.3 ml/cm(3) to 1.4±0.3 ml/cm(3)). In the APit, an increase of Mn(2+) uptake led to an increase in K(i) (from 0.034±0.009 min(-1) to 0.049±0.012 min(-1)) while a decrease of Mn(2+) uptake corresponded to a decrease in K(i) (from 0.034±0.009 min(-1) to 0.019±0.003 min(-1)). This work demonstrates that graphical analysis applied to dMEMRI data can quantitatively measure changes to Mn(2+) uptake following modulation of neural activity.

    View details for DOI 10.1016/j.neuroimage.2011.12.030

    View details for Web of Science ID 000301218700040

    View details for PubMedID 22227885

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