AtlasGuide: Software for stereotaxic guidance using 3D CT/MRI hybrid atlases of developing mouse brains

Li, Xin; Hsu, Johnny; Jiang, Hangyi; Mori, Susumu

doi:10.1016/j.jneumeth.2013.08.017

Cited by 16 publications

(12 citation statements)

References 23 publications

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“…These targeting inaccuracies may be caused by different factors, such as the stereotactic device, operator experience, inter-animal variability, the use of standard reference atlases, etc 1926…”

Section: Discussionmentioning

confidence: 99%

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Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

Rangarajan

Velde

Gent

et al. 2016

Sci Rep

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Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study.Stereotactic neurosurgery is used to introduce a needle or an electrode at a precise location in the brain, for instance to perform deep brain stimulation (DBS), lesioning (e.g. ablation) or cell-based therapy in patients to ameliorate symptoms of neurological disease. Clinical use of stereotactic neurosurgery benefits from experimental research on rodent models, for instance to identify potential target regions. Likewise, small animal investigations like DBS for neuromodulation 1,2 , electrochemical/ electrolytic lesioning for creating animal models or ameliorating symptoms 3,4 , as well as gene therapy investigations involving injection of stem cells/therapeutic agents/tracers 5-7 requires stereotactic brain surgery. They rely on standard stereotaxic brain atlases (e.g. The rat brain in stereotaxic coordinates (George Paxinos and Charles Watson, Academic Press, 2006 8 ) and skull landmarks (e.g. bregma (B), lambda (L)) for localizing the target in the rodent brain and for surgery planning 9 . Stereotaxic frames used in small animal brain surgery have species-specific head mounting platforms, with a manipulator that can move in three dimensions along the axes with respect to the head holder. The targeting accuracy of such devices is dependent on numerous factors, such as inter-animal anatomical variability, positioning errors (e.g. skull flat position), scaling errors (e.g. when using the same atlas with animals of a different size or strain), errors in intra-operative localization of bregma, operator-specific deviations etc. Some of these sources of inaccuracy in small animal stereotactic surgery have been characterized in previo...

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Section: Discussionmentioning

confidence: 99%

“…The need and benefits of image-based pre-operative surgery planning in small animals has been previously reported in several studies2526272829. However, several challenges still remain with respect to using imaging for prospective planning and/or retrospective assessment of stereotactic neurosurgery in animal models.…”

mentioning

confidence: 99%

Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

Rangarajan

Velde

Gent

et al. 2016

Sci Rep

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“…An aspect often missing in published brain atlases obtained from serial histology is the localization of anatomical reference points. For example, many neurophotonics studies localize the imaging position according to skull-based reference points such as the bregma and lambda points [150][151][152]. Thus, keeping track of the precise position of an acquired brain within the animal skull would enable neuroscientists to access the serial histological data more reliably.…”

Section: Tissue Preparation and Cutting Artefactsmentioning

confidence: 99%

A Review of Intrinsic Optical Imaging Serial Blockface Histology (ICI-SBH) for Whole Rodent Brain Imaging

2019

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In recent years, multiple serial histology techniques were developed to enable whole rodent brain imaging in 3-D. The main driving forces behind the emergence of these imaging techniques were the genome-wide atlas of gene expression in the mouse brain, the pursuit of the mouse brain connectome, and the BigBrain project. These projects rely on the use of optical imaging to target neuronal structures with histological stains or fluorescent dyes that are either expressed by transgenic mice or injected at specific locations in the brain. Efforts to adapt the serial histology acquisition scheme to use intrinsic contrast imaging (ICI) were also put forward, thus leveraging the natural contrast of neuronal tissue. This review focuses on these efforts. First, the origin of optical contrast in brain tissue is discussed with emphasis on the various imaging modalities exploiting these contrast mechanisms. Serial blockface histology (SBH) systems using ICI modalities are then reported, followed by a review of some of their applications. These include validation studies and the creation of multimodal brain atlases at a micrometer resolution. The paper concludes with a perspective of future developments, calling for a consolidation of the SBH research and development efforts around the world. The goal would be to offer the neuroscience community a single standardized open-source SBH solution, including optical design, acquisition automation, reconstruction algorithms, and analysis pipelines.

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“…Genetically modified mice have proven to be a vital tool in preclinical research; however, the wide variety of strains have a diversity of neuroanatomical differences, including brain proportions, which in‐turn decreases considerably the stereotaxic accuracy . With neuroanatomical proportion differences and scaling functions based on mouse size, it is difficult to determine the accuracy of atlas based stereotaxic targeting . Other limitations of mouse brain atlases include lack of detailed neonatal atlases, the potential for inaccuracy during tissue sectioning and fixation of brain pathology slices, and the limited number of slice orientations available, which increases the difficulty of designing oblique needle paths to avoid damaging sensitive neuroanatomical structures .…”

Section: Introductionmentioning

confidence: 99%

“…With neuroanatomical proportion differences and scaling functions based on mouse size, it is difficult to determine the accuracy of atlas based stereotaxic targeting . Other limitations of mouse brain atlases include lack of detailed neonatal atlases, the potential for inaccuracy during tissue sectioning and fixation of brain pathology slices, and the limited number of slice orientations available, which increases the difficulty of designing oblique needle paths to avoid damaging sensitive neuroanatomical structures . Recently, pre‐operative MR and micro‐CT images have been combined with pathology slices to create more accurate reference atlases .…”

Section: Introductionmentioning

confidence: 99%

An ultra‐high field strength MR image‐guided robotic needle delivery system for in‐bore small animal interventions

2017

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Purpose: The purpose of this study was to develop and validate an image-guided robotic needle delivery system for accurate and repeatable needle targeting procedures in mouse brains inside the 12 cm inner diameter gradient coil insert of a 9.4 T MR scanner. Many preclinical research techniques require the use of accurate needle deliveries to soft tissues, including brain tissue. Soft tissues are optimally visualized in MR images, which offer high-soft tissue contrast, as well as a range of unique imaging techniques, including functional, spectroscopy and thermal imaging, however, there are currently no solutions for delivering needles to small animal brains inside the bore of an ultrahigh field MR scanner. This paper describes the mechatronic design, evaluation of MR compatibility, registration technique, mechanical calibration, the quantitative validation of the in-bore image-guided needle targeting accuracy and repeatability, and demonstrated the system's ability to deliver needles in situ. Methods: Our six degree-of-freedom, MR compatible, mechatronic system was designed to fit inside the bore of a 9.4 T MR scanner and is actuated using a combination of piezoelectric and hydraulic mechanisms. The MR compatibility and targeting accuracy of the needle delivery system are evaluated to ensure that the system is precisely calibrated to perform the needle targeting procedures. A semi-automated image registration is performed to link the robot coordinates to the MR coordinate system. Soft tissue targets can be accurately localized in MR images, followed by automatic alignment of the needle trajectory to the target. Intra-procedure visualization of the needle target location and the needle were confirmed through MR images after needle insertion. Results: The effects of geometric distortions and signal noise were found to be below threshold that would have an impact on the accuracy of the system. The system was found to have negligible effect on the MR image signal noise and geometric distortion. The system was mechanically calibrated and the mean image-guided needle targeting and needle trajectory accuracies were quantified in an image-guided tissue mimicking phantom experiment to be 178 AE 54 lm and 0.27 AE 0.65°, respectively. Conclusions: An MR image-guided system for in-bore needle deliveries to soft tissue targets in small animal models has been developed. The results of the needle targeting accuracy experiments in phantoms indicate that this system has the potential to deliver needles to the smallest soft tissue structures relevant in preclinical studies, at a wide variety of needle trajectories. Future work in the form of a fully-automated needle driver with precise depth control would benefit this system in terms of its applicability to a wider range of animal models and organ targets.

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AtlasGuide: Software for stereotaxic guidance using 3D CT/MRI hybrid atlases of developing mouse brains

Cited by 16 publications

References 23 publications

Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

A Review of Intrinsic Optical Imaging Serial Blockface Histology (ICI-SBH) for Whole Rodent Brain Imaging

An ultra‐high field strength MR image‐guided robotic needle delivery system for in‐bore small animal interventions

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