What is multimodal imaging and why ย it is important?
Problem:
No single imaging technology can provide holistic information about aย given sample. This limitation can be overcome by combining multiple imagingย technologies, which gathers information about the specimen with two or more complementary modalities that โ sequentially combined โ create a composite view of the sample.
Solution:
Correlated multimodal imaging (CMI) helps to bridge the gap between biological and pre-clinical imaging.
One important aim of multimodal imaging is to span all relevant resolutionย ranges from molecules to organisms for the biomedical question ofย interest. Integrative approaches and multiscale imaging can provide aย mechanistic understanding of diseases and organisms by addingย structural information about relevant molecular machines and molecules,ย and by deciphering underlying molecular mechanisms.
Our showcase studies.
2
modalities
ยตMRI + HREM
High-throughput phenotyping of murine embryos
Rapid and precise phenotyping analysis of large numbers of wild-type and mutant mouse embryos is essential for characterizing the genetic and epigenetic factors regulating embryogenesis. The combination of high-throughput ยตMRI with HREM provides an alternative screening pipeline with advantages over existing 3D phenotype screening methods as well as traditional histology. We highly recommend the ยตMRI-HREM phenotype analysis pipeline as a routine tool for analysing the phenotype of transgenic and mutant embryos.
Source (PubMed): Pieles et al., Journal of Anatomy, 2007 [17532797]
Image:ย 3D volume HREM rendering of a mouse embryo. Source: DMM, 2014 Oct.
2
modalities
MALDI MS + ยตXRF
Lipid distribution in the bone
We examined specific lipid distributionsย in skin, cartilage, muscle, nail, and the intact morphology of bone by calcium and phosphorusย imaging. A combination of molecular and elemental imaging was achieved, providing now for theย first time the possibility of gathering MALDI MSI and ฮผXRF information from the very same sample withoutย any washing steps omitting therefore the analytical artifacts that inevitably occur in approaches usingย consecutive tissue sections. The proposed combination can benefit in research studies regarding boneย diseases, osteoporosis, osteoarthritis, cartilage failure, bone/tendon distinguishing, where elemental andย lipid interaction play an essential role.
Source (PubMed): Svirkova et al., Analyst, 2018 [29737333]
Imagesย show the distribution of Ca, P, and ROI data obtained from sample fixed to a glass slide with double-sided tape.
2
modalities
PAT + OCT
In vivo human skin structure and vasculature imaging
Cutaneous blood flow accounts for approximately 5% of cardiac output in human and plays a key role in a number of a physiological and pathological processes. We show for the first time a multi-modal photoacoustic tomography (PAT), optical coherence tomography (OCT) and OCT angiography system with an articulated probe to extract human cutaneous vasculature in vivo in various skin regions. OCT angiography supplements the microvasculature which PAT alone is unable to provide.ย This multimodal system is a valuable tool for comprehensive non-invasive human skin vasculature and morphology imaging in vivo.
Source (PubMed): Liu et al., Biomedical Optics Express, 2016 [27699106]
Image:ย (A) OCT morphologic volume showing the skin creases.ย The inlet is a photo of the knee imaged with the dashed square indicating approximately the scanned region. (B)ย A slice in the dermal-epidermal junction giving PAT in green and OCT angiography in red. Source: Biomedical Optics Express.
3
modalities
ยตMRI + ยตCT + HREM
Multiscale murine tumore vasculature
Tumour vasculature plays a major role for tumour progression and dissemination,ย highlighting the importance of vascular visualisation. The application of CMI pipelinesย allowed the acquisition of a comprehensive set of vascular parameters for a single tumor. The workflow visualizes capillaries at different length scales, puts them into the context of the overall tumor vessel network and allows quantification and comparison of vessel densities and morphologies by different modalities. The workflow adds information about hypoxia and blood flow rates.
Source (PubMed): Zopf et al., Molecular Imaging and Biology, 2021[34101107]
Image:ย Co-registration of the vasculature as segmented based on microMRI, microCT, and HREM datasets.
4
modalities
ยตCT + AFM + SEM + XRF
Cross-modality imaging of murine jawbones
Bisphosphonates (BIS) have many positiveย systemic effects in patients suffering fromย rheumatologic disorders, but a severe localย side effect: โBIS-related osteo-necrosis ofย the jawโ (BRONJ) can develop after invasiveย dental procedures in patients receivingย chronic BIS therapy. The exactย pathomechanism of BRONJ is not known,ย but alleviation of tissue regenerationย processes may prevent development ofย BRONJ. Low level light therapy and shockย therapy are promising clinical approaches.ย Here we intend to elaborate the therapeuticย potential of these physical approaches inย BRONJ with emphasis on theย pathomechanism.
Source (PubMed): Reier et al., Analyst, 2021 [27699106]
Image: Synopsis of the CMI workflow to visualize multiparametric jawbone features for the clinically relevant murine model.
4
modalities
ยตMRI + OCT/PAT + ยตCT + HREM
Blood vessel tracking
Spatial information on vascular anatomy is aย prerequisite for answering key questions inย a variety of life-science disciplines. Analysisย of vascular structures, tracking of oxygenย and drug transport, changes in wall stressย and similar investigations all rely on aย precise 3D description of vascularization.ย Retrieval of the precise anatomy from a 3Dย digital image, i.e. image segmentation, is aย task known to be time demanding, errorproneย and unintuitive for humans. The aimย of this project is a vessel tracking algorithm,ย that can be applied for segmentation inย various vascularization environments,ย across a wide range of spatial scales, and aย broad diversity of modalities.
6
modalities
ยตMRI + OCT/PAI + ยตCT + HREM + HISTO + MSI
Angiogenesis in tumors
Cancer is the second leading cause ofย mortality in Europe. Activating angiogenesis,ย the sprouting of new blood vessels from theย existing vasculature, is one of the hallmarksย of cancer and facilitates rapid tumor growthย and metastasis. Thus, inhibiting tumor neoangiogenesisย is a strategy for cancerย treatment currently being pursued. Currentย anti-angiogenic therapies are only based onย the inhibition of tyrosine kinase receptorsย (RTK). We aim to study how RTK inhibitorsย affect the structure and function of tumorย vessels and their microenvironment, and toย identify new blockers that can potentiate theย anti-cancer effects of current anti-angiogenicย therapies.
Image:ย MRI (15.2 T) of a subcutaneous mouse tumor & blood vesselย network of isolated tumor
7
modalities
PET + ยตMRI + ยตCT + HISTO + Confocal + MSI + XRF
Micro-calcifications in aortae
The detection of sites of vascular calcification in the blood system may beย used as an early prognostic marker for cardiovascular diseases. Typically,ย these calcifications are quantified in patients using CT. Recently ex-vivoย experiments showed that the PET-tracer 18F-NaF is able to bindย selectively to micro-nodules of pathological calcification. In contrast to theย glucose analogue 18F-FDG, this binding occurs at high image contrastย and is highly specific for sites of calcification. In the pilot project, we aim toย investigate if small-animal PET with 18F-NaF is able to detect vascularย calcification in the thoracic aorta of male Sprague-dawley rats. Arteryย calcification will be induced by feeding rats with a low-protein/highadenineย diet. Baseline 18F-NaF-PET and sequential MRI/PET scans willย be performed after the 3 week-diet period. After final imaging, animals willย be euthanized and thoracic aortas will be removed for further analysis.
Image: Multimodal imaging to quantify calcification of blood aortae.