Landau Lab

Methods/Imaging methods and biological validation

From signal to evidence

No single measurement tells the whole story. We combine PET and quantitative autoradiography with behavioural testing and analyses of brain tissue — so that each can test, sharpen or explain what the others show.

PETAutoradiographyTissue analysesBehaviourRodents & minipigs
Three overlapping circles — in vivo PET, autoradiography and tissue analyses, and behaviour. Where they overlap is where evidence is strongest. IN VIVO PET THE LIVING BRAIN AUTORADIOGRAPHY & TISSUE BEHAVIOUR FUNCTION evidence

01 Our approach

Understanding what imaging signals represent

We investigate how brain disorders and treatments affect molecular signalling and brain function, with a particular focus on Parkinson's disease and depression.

Using positron emission tomography (PET) and quantitative autoradiography in rodents and minipigs, we study molecular targets in the living brain and in brain tissue. We combine imaging with behavioural testing and neurochemical, molecular and histological analyses to understand what imaging signals represent biologically and how they change with disease and treatment.

These methods are not steps in a fixed sequence. Which one comes first depends on the question — and a study often returns to an earlier method once another has raised a new question.

  • Start in tissue

    Map where a tracer binds, and check that the binding is specific, at high resolution on brain sections — then take it into the living brain. This is how we are approaching GPR6. GPR6 →

  • Start in the living brain

    Follow a change over time with PET in the same animal, then ask in tissue what it reflects. In rat lesion models, [11C]UCB-J PET and [3H]UCB-J autoradiography found closely matching losses of SV2A binding. Synaptic imaging →

  • Start with function

    Begin with an intervention and a behavioural read-out, then look for its molecular correlates. In a rat Parkinson's model, treadmill exercise was followed by pain-threshold testing and autoradiography of four targets, including SV2A and TSPO. Synaptic imaging →

Loss of SV2A binding, lesioned vs intact side

20 µg QA39.3%38.4%
40 µg QA55.1%52.5%

[11C]UCB-J PET, living brain[3H]UCB-J autoradiography, sections

Validation example

PET and tissue agree, when tested

In rats with a one-sided striatal lesion, [11C]UCB-J PET in the living brain and [3H]UCB-J autoradiography of brain sections measured closely matching losses of SV2A binding. Checking the PET signal against tissue is how we interpret it; in minipigs, agreement depended mainly on grey–white matter contrast, so it is tested region by region.

Thomsen et al., J Cereb Blood Flow Metab 2021 · doi:10.1177/0271678X20931140 · redrawn from Table 2; QA, quinolinic acid · Thomsen et al., Mol Imaging Biol 2020 · doi:10.1007/s11307-020-01506-8

02 The methods

One page for each method

What each method measures, what it does well, and what it cannot show on its own.

In vivoPETImaging the living brain over timeRead →Ex vivoAutoradiography & tissue analysesBinding on brain sections, at fine detailRead →Ex vivoReal-time autoradiographyHow the BeaQuant reads tritium tracers on brain sections in hoursRead →FunctionBehaviourWhat animals do, linked to molecular changeRead →ModelsRodents and minipigsChoosing the model for the questionRead →PapersMethods papersSelected methods and validation work, at the end of this page.Jump ↓

03 How they fit together

Start from the question, not the method

Choose a question to see which measurements answer it, how they check one another, and an example from our published work.

    PETLIVING BRAIN TissueAUTORADIOGRAPHY& ANALYSES BehaviourFUNCTION OTHERMEASURES No arrows: any measurement can come first.

    04 Collaborations

    An integrated platform

    Our platform brings together PET, quantitative autoradiography, behavioural testing and analyses of brain tissue. Collaborations in radiochemistry, MRI, molecular biology, histology and neurosurgery support tracer development and validation, experimental interventions and interpretation of imaging findings.

    RadiochemistryMRIMolecular biologyHistologyNeurosurgery

    This integrated approach connects molecular measurements with brain function, behaviour and treatment effects.

    05 Methods papers

    Selected methods and validation work

    1. 2023
      Combined in vivo microdialysis and PET studies to validate [11C]yohimbine binding as a marker of noradrenaline releasePET · microdialysis
      Landau AM, Jakobsen S, Thomsen MB, … Doudet DJ · Biomolecules
    2. 2021
      In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PETPET · autoradiography
      Thomsen MB, Jacobsen J, Lillethorup TP, … Brooks DJ, Landau AM · Journal of Cerebral Blood Flow & Metabolism
    3. 2020
      Preclinical PET studies of [11C]UCB-J binding in minipig brainPET · autoradiography
      Thomsen MB, Schacht AC, Alstrup AKO, … Brooks DJ, Landau AM · Molecular Imaging and Biology
    4. 2021
      Exercise protects synaptic density in a rat model of Parkinson's diseaseAutoradiography · behaviour
      Binda K, Lillethorup T, Real C, … Chacur M, Landau A · Experimental Neurology
    5. 2015
      Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivoPET · kinetic modelling
      Phan JA, Landau AM, Wong DF, … Doudet DJ, Gjedde A · Journal of Cerebral Blood Flow & Metabolism
    6. 2022
      Quantitative assessment of motor function in minipig models of neurological disorders using a pressure-sensitive gait matMethods
      Steinmüller JB, Binda KH, Lillethorup TP, … Sørensen JCH, Glud AN · Journal of Neuroscience Methods
    7. 2020
      Type of anaesthetic influences [11C]MDL100,907 binding to 5HT2A receptors in porcine brainMethods
      Landau AM, Noer O, Alstrup AKO, … Doudet DJ, Winterdahl M · Molecular Imaging and Biology
    8. 2013
      Effects of anesthesia and species on the uptake or binding of radioligands in vivo in the Göttingen minipigMethods
      Alstrup AKO, Landau AM, Holden JE, … Doudet DJ · BioMed Research International
    9. 2023
      Selecting the best animal model of Parkinson's disease for your research purpose: insight from in vivo PET imaging studiesReview
      Real CC, Binda KH, Thomsen MB, Lillethorup TP, Brooks DJ, Landau AM · Current Neuropharmacology

    All publications: publication list →

    Questions for review

    1. Are these the right example studies to feature, or would you prefer others?
    2. Which equipment and facilities should the page name — and which belong to shared facilities or collaborators?
    3. Do you have photos of behavioural testing, the scanners or the lab that we could use?

    The methods at work · four research themes

    01Dopamine signalling and GPR6Starting in tissue: tools to measure GPR6 binding and drug engagement.Visit → 02Synaptic imagingHow disease and treatments change SV2A binding, measured with UCB-J PET and autoradiography.Visit → 03Brain stimulation and neuromodulationScan, stimulate, scan again: DBS, VNS and electroconvulsive stimulation.Visit → 04Neuroinflammation and glial responsesDeveloping and validating new tracers, checked from the living brain to the cells themselves.Visit →