Ověřování biochemických a farmakologických vlastností ... · 1st Faculty of Medicine,...

Neuroimaging I:

1st Faculty of Medicine, Charles University in Prague Center for Advanced Preclinical Imaging (CAPI)

1st Faculty of Medicine, Charles University in Prague

Center for Advanced Preclinical Imaging (CAPI)


Center for Advanced Preclinical Imaging (CAPI) [email protected]

Shoghi-Jadid et al., 2002



NeuroimagingObtaining evidence from the brain

• Lesion studies – stroke, trauma (PET, SPECT, CT, MRI)

• Cerebral blood flow (PET, SPECT, CT, MRI)

• Neurotransmitter Imaging (PET, SPECT, fMRI)

• Neuro-Receptor Imaging (PET, SPECT)

• Dissease specific Imaging (Multimodal)



Neuroimaging“The Big 10”

• Infarction

• Hemorrhage

• Infection

• Tumor

• Trauma

• Dementia

• MS

• Epilepsy

• Cranial neuropathy

• Orbits / Ophtho dx



NeuroimagingImaging Approaches

Structural Functional

X-ray

MRI

CT/CAT

fMRI

PET

SPECT

EEG ECG

PET/CT

SPECT/CT

PET/MRI

Multimodal



Anatomical Brain Imaging



Anatomical Brain ImagingCT

Hyperdense MCA Insular Ribbon Lentiform Nucleus

CT Signs in Early MCA Ischemia



Anatomical Brain ImagingStructural MRI

• Essential in clinical care

• Radiologists perform qualitative “lightbox”

reads

• Most psychiatric and neurological

disorders are invisible to reading

radiologists



Anatomical Brain ImagingT1 MRI

designed (timing of radio pulses and data readout) to produce contrastbetween gray matter, white matter, and CSF

Spatial resolution: ca. 1 mm3, Acquisition time for whole head is 5-10 minutes



Anatomical Brain ImagingT1 MRI – Image Zoom

• Can follow GM cortex fairly well

– Can measure thickness of

cortex and try to quantify vs

age and/or disease and/or

genes

• Bright spots and lines: arterial

inflow artifact

– Leads to idea of MRA =

Magnetic Resonance

Angiography = acquire

images to make arteries

stand out even more

• Higher spatial resolution is

possible

– At the cost of scan time



Anatomical Brain ImagingT2 MRI

Often better than T1-weighting in detecting tumors and infarcts

(usually radiologists look at both types of scans)

T1 weighted T2 weighted



Anatomical Brain ImagingT2* MRI

Designed to make venous blood (with lots of deoxy-hemoglobin)

darker than normal tissue = venography

Output image minIP ± 1 slice minIP ± 2 slices



Anatomical Brain ImagingContrast enhanced MRI

T2-weighted post-contrast T1-weighted

Tumor Seizure Patient

Gd-enhanced

T1-weighted

Gd-enhanced

T2*-weighted



Functional Brain Imaging



Functional Brain ImagingEnergy Metabolism 18F-FDG

Normal Multiple Infarct

Dementia

Huntington's

Normal Alzheimer's Pick's



Functional Brain ImagingEnergy Metabolism 18F-FDG



Functional Brain ImagingNeurotransmitter 18F-FDOPA



Functional Brain ImagingAmino Acid Transport

Imaging of 49-y-old woman who had been previously treated for glioblastoma

multiforme with tumor resection and conventional radiotherapy at dose of 60 Gy. (A)

T1-weighted MR image with contrast medium, obtained 13 mo after initial surgery,

showing contrast-enhanced lesion in left frontal lobe. (B) 11C-MET PET image

showing obvious accumulation of tracer corresponding to abnormality on MR image.

L/Nmeanwas 1.70. Recurrent tumor was pathologically confirmed by second surgery.



Zubieta et al. - Journal of Cerebral Blood Flow & Metabolism (1998) 18, 619–631

Functional Brain ImagingAmino Acid Transport – Glycine transporter 1

[11C]GSK931145 distribution in a healthy volunteer

Pig Primate Human



Neuroreceptor Imaging



Selected Receptor Tracers



Neuro-Receptor ImagingDAT – dopamine transporter



11C-DTBZ K1 and 18F-FDG images at 3 brain levels for one representative subject from each group. Robert A. Koeppe et al. J Nucl Med 2005;46:936-944

Neuro-Receptor ImagingVMAT2 – vesicular monoamine transporter type 2



Neuro-Receptor Imaging5-HT2A receptor

Horizontal PET images showing the uptake of [11C]NMSP in the frontal cortex at the level of the basal ganglia at baseline, and after the administration of 2 mg, 10 mg and 100 mg oral doses of an inverse agonist (ACP-103)



microPET and autoradiography studies of PRG/PRP imaging of gene expression in the same mouse. PRG is D2 receptor, and PRPis FESP. (Left) MicroPET image of a single 1.5-mm-thick longitudinal section of living control mouse negative for D2 receptor (D2

−)PRG, showing no significant retention of PRP in liver (dashed lines). In animal carrying dopamine receptor reporter gene (D2

+),there is retention of FESP PET reporter probe in liver reflecting gene expression. Images were taken 50 min after injection of FESPand 2 days after virus administration. (Right) After microPET imaging, animals were killed, sectioned, and imaged withautoradiography

Michael E. Phelps PNAS 2000;97:9226-9233

Neuro-Receptor ImagingD2 receptor – 11c-Fluorethylspiperone (FESP)



Neuro-Receptor ImagingGABAA-benzodiazepine receptor

Magnetic resonance imaging (MRI) and delayed-activity positron emission tomography (PET)

with [11C]flumazenil and single photon emission computed tomography (SPECT) with [123I]iomazenil

images of one subject at different anatomic levels

Millet et al.; Journal of Cerebral Blood Flow & Metabolism (2000) 20, 1587–1603



Neuro-Receptor ImagingOpioid Receptor

PET scan of a six month old rhesus macaque using a [C-11]diprenorphine tracer,

specific for opioid receptors.



Neuro-Receptor ImagingMuscarinic Receptor

Quantification of muscarinic cholinergic receptors with [11C]N-methyl-4-piperidyl benzylate ([11C]NMPB) -

distribution parameters and activity

Zubieta et al. - Journal of Cerebral Blood Flow & Metabolism (1998) 18, 619–631



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