What is QUINT?

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The QUINT workflow is an analysis solution for rodent brain microscopy data, enabling brain-wide mapping and regional quantification using a reference brain atlas. It combines the use of several software with graphical user interfaces (GUI), no coding ability required.

As input, the QUINT workflow takes images of brain sections and as output generates counts of labelled objects, percentage coverage per atlas-region, and point clouds for visualising labelling in 3D atlas space.

It currently supports quantification relative to the following atlases:

  • Allen Mouse Brain Atlas Common Coordinate Framework version 3 (2015 and 2017) (CCFv3)

  • Waxholm Atlas of the Sprague Dawley rat, version 2, 3 and 4 (WHS rat brain atlas).

  • Kim Unified Mouse Brain Atlas version 1 (2019)

  • Developmental Mouse Brain Atlas (DeMBA, day 4-56)

QUINT involves several defined steps:

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  1. Prepare images for analysis using Nutil or another image editing tool (rename the files to meet the QUINT file naming convention and downscale).

  2. Register to an atlas using QuickNII, VisuAlign and/or DeepSlice. Linear registration is performed using QuickNII, then VisuAlign enables refinement of the registration using non-linear methods. For coronal mouse brain sections, DeepSlice can automate the linear registration step.

  3. Extract features using ilastik or another image analysis tool.

  4. Quantify features with Nutil.

  5. Perform quality control with QCAlign. This is an optional step that allows quality control of the section images and quality control of the atlas-registration. It also enables exploration of the atlas hierarchy and creation of a customized hierarchy level to use for the quantification.

  6. Visualise the results in 3D with the MeshView Atlas Viewer.

Watch our video tutorial


Examples of use

QUINT is suited for histological sections from mouse and rat brain that have been labelled to reveal features. It works for sections cut at any angle of orientation, for complete as well as partial brain sections, and for sections affected by distortions. It can be used for:

  • Cell count analysis

  • To spatially characterise pathology

  • Analyse tract tracing connections

Check out the following articles that have used QUINT:

  • Lubben N et al. LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression. Translational Neurodegeneration. March 2024. http://doi.org/10.1186/s40035-024-00403-2

  • Geertsma et al. A topographical atlas of alpha-Synuclein dosage and cell-type expression in the adult mouse brain and peripheral organs. npj. March 2024. https://doi.org/10.1038/s41531-024-00672-8

  • Koen Seignette, Nora Jamann, Paolo Papale, Huub Terra, Ralph O Porneso, Leander de Kraker, Chris van der Togt, Maaike van der Aa, Paul Neering, Emma Ruimschotel, Pieter R Roelfsema, Jorrit S Montijn, Matthew W Self, Maarten HP Kole, Christiaan N Levelt. Jan 2024. Experience shapes chandelier cell function and structure in the visual cortex eLife 12:RP91153. https://doi.org/10.7554/eLife.91153.3

  • Guardamagna M, Chadney O, Stella F, Zhang Q, Kentros C, Battaglia F. Direct Entorhinal Control of CA1 Temporal Coding. bioRxiv. May 2023; doi: https://doi.org/10.1101/2023.05.27.542579

  • Goralski T et al. Spatial transcriptomics reveals molecular dysfunction associated with Lewy pathology. BioRxiv. May 2023. https://doi.org/10.1101/2023.05.17.541144

  • Zhang G, Xia S, Zhang N, Gao F, Zlokovik B, Zhang L, Zhao Z, Tao H. Integrative mapping of spatial transcriptomic and amyloid pathology in Alzheimer’s disease at single-cell resolution. Preprint. May 2023. https://doi.org/10.1101/2023.05.07.539389

  • Gurdon B, Yates SC, Csucs G, Groeneboom N, Hadad N, Telpoukhovskaia M, Oullette A, Oullette T, O’Connell K, Singh S, Murdy T, Merchant E, Bjerke I, Kleven H, Schlegel U, Leergaard T, Puchades M, Bjaalie J, Kaczorowski C. Detecting the effect of genetic diversity on brain composition in an Alzheimer’s disease mouse model. BioRxiv. Feb 2023. https://doi.org/10.1101/2023.02.27.530226

  • Hug NF, Lindsay NM, McCallum WM, Bryan J, Huang K, Ochadarena N, Tassou A, Scherrer G. Opioid receptor architecture for the modulation of brainstem functions. 2022 Dec. BioRxiv. https://doi.org/10.1101/2022.12.24.521865

  • Lopes MM, Paysan J, Rino J, Lopes SM, Pereira de Almeida L, Cortes L, Nobre RJ. A new protocol for whole-brain biodistribution analysis of AAVs by tissue clearing, light-sheet microscopy and semi-automated spatial quantification. Gene Ther. 2022 Nov 1. https://doi.org/10.1038/s41434-022-00372-z.

  • Jo Y, Lee SM, Jung T, Park G, Lee C, Im GH, Lee S, Park JS, Oh C, Kook G, Kim H, Kim S, Lee BC, Suh GSB, Kim SG, Kim J, Lee HJ. General-Purpose Ultrasound Neuromodulation System for Chronic, Closed-Loop Preclinical Studies in Freely Behaving Rodents. Adv Sci (Weinh). 2022 Oct 19:e2202345. https://doi.org/10.1002/advs.202202345

  • Botros P, Vendrell-Llopis N, Costa R, Carmena J. A neural model of proximity to reward. 2022 Oct. BioRxiv 2022.10.03.510669. https://doi.org/10.1101/2022.10.03.510669

  • Yao Y, Barger Z, Saffari Doost M, Tso CF, Darmohray D, Silverman D, Liu D, Ma C, Cetin A, Yao S, Zeng H, Dan Y. Cardiovascular baroreflex circuit moonlights in sleep control. Neuron. 2022 Sep 23:S0896-6273(22)00802-9. https://doi.org/10.1016/j.neuron.2022.08.027.

  • Ham GX, Augustine GJ. Topologically Organized Networks in the Claustrum Reflect Functional Modularization. Frontiers in Neuroanatomy. 16 June 2022. https://doi.org/10.3389/fnana.2022.901807

  • Bjerke IE, Cullity ER, Kjelsberg K, Charan KM, Leergaard TB, Kim JH. DOPAMAP, high-resolution images of dopamine 1 and 2 receptor expression in developing and adult mouse brains. Sci Data. 2022 Apr 19;9(1):175. https://doi.org/10.1038/s41597-022-01268-8

  • Telpoukhovskaia MA et al. Conserved cell-type specific signature of resilience to Alzheimer’s disease nominates role for excitatory cortical neurons. bioRxiv; doi: https://doi.org/10.1101/2022.04.12.487877

  • Tocco C, Øvsthus M, Bjaalie J.G, Leergaard T.B and Studer M. The topography of corticopontine projections is controlled by postmitotic expression of the area-mapping gene Nr2f1. Development; 149 (5). 2022. https://doi.org/10.1242/dev.200026

  • Kim S, Jo Y, Kook G, Pasquinelli C, Kim H, Kim K, Hoe HS, Choe Y, Rhim H, Thielscher A, Kim J, Lee HJ. Transcranial focused ultrasound stimulation with high spatial resolution. Brain Stimul. 2021 Mar-Apr;14(2):290-300. https://doi.org/10.1016/j.brs.2021.01.002

  • Whilden CM, Chevée M, An Seong Yeol, Pezon Brown S. The synaptic inputs and thalamic projections of two classes of layer 6 corticothalamic neurons in primary somatosensory cortex of the mouse. J Comp Neurol. 2021 Dec;529(17):3751-3771. doi: https://doi.org/10.1002/cne.25163. Epub 2021 May 6.

  • McDonald MW, Jeffers MS, Filadelfi M, Vicencio A, Heidenreich G, Wu J and Silasi G. Localizing Microemboli within the Rodent Brain through Block-Face Imaging and Atlas Registration. eNeuro 16 July 2021, 8 (4) ENEURO.0216-21.2021; DOI: https://doi.org/10.1523/ENEURO.0216-21.2021

  • Bjerke IE, Yates SC, Laja A, Witter MP, Puchades MA, Bjaalie JG and Leergaard TB. Densities and numbers of calbindin and parvalbumin positive neurons across the rat and mouse brain. 2021, iScience.https://doi.org/10.1016/j.isci.2020.101906