Imaging Inflammation - From Whole Body Imaging to Cellular Resolution

Abstract

Imaging techniques have evolved impressively lately, allowing whole new concepts like multimodal imaging, personal medicine, theranostic therapies, and molecular imaging to increase general awareness of possiblities of imaging to medicine field. Here, we have collected the selected (3D) imaging modalities and evaluated the recent findings on preclinical and clinical inflammation imaging. The focus has been on the feasibility of imaging to aid in inflammation precision medicine, and the key challenges and opportunities of the imaging modalities are presented. Some examples of the current usage in clinics/close to clinics have been brought out as an example. This review evaluates the future prospects of the imaging technologies for clinical applications in precision medicine from the pre-clinical development point of view.

Keywords: MRI; Optical coherence tomography (OCT); PET; SPECT; Two-Photon microscopy (TPM); hyperpolarization; optical imaging; precision medicine.

Figure 1

Digital subtraction angiography of the brain with injection in the right internal carotid artery in a patient with varicella-zoster vasculitis (left). Multiple stenoses in the M1 segment of the right middle cerebral artery were found (arrows). 3T MR vessel wall imaging (right) shows strong contrast enhancement of the corresponding segments (arrows). The inset shows a transverse section through the proximal M1 segment with circumferential wall enhancement pattern.

Figure 2

Postcontrast 3T MR vessel wall imaging of a 5 mm aneurysm at the middle cerebral artery bifurcation. Note the strong wall enhancement (arrows) as a possible marker for visualization of wall inflammation.

Figure 3

MRI in patient with active CD involving the ileum: there is bowel wall thickening in T2w sequence (A) and increased contrast media uptake in T1w, fat suppressed imaging (B). Inflammation is also revealed by hyperintensity in DWI (C).

Figure 4

Measuring the metabolism of an arthritis model with hyperpolarized hyperpolarized MRI: anatomical 1H MRI (top left), quantitative metabolic map of lactate-to-pyruvate ratio (top right) and corresponding 13C spectra. Arthritis was induced in the right paw of the rats while the left served as a control. Hyperpolarized pyruvate was injected and ¹³C metabolic imaging performed. The inflamed paw exhibited a 65% increase in lactate signal and no alanine signal indicating abnormal metabolism. Figure modified from [MacKenzie et al. (79)].

Figure 5

Ventilation imaging of the diseased human lung using ¹²⁹Xe-MRI. Coronal ventilation images were acquired in subjects with asthma (upper row), COPD (middle row), or cystic fibrosis (lower row). Numerous ventilation defects can be seen in each of the images secondary to airflow obstruction caused by the underlying diseases. Figure taken from Mugler, J. P. et al., Journal of Magnetic Resonance Imaging (85).

Figure 6

Slide-free image of a bulk porcine skin sample stained with acridine orange and sulforhodamine 101. Zoom-ins show a hair follicle (top) and a sweat duct (bottom). Total acquisition took 13 minutes plus. 10 minutes processing time.

Figure 7

(A) HE stained histology of the imaged sample at different location (I) cornified layer, (II) granular & spinous layers, (III) basal layers, (IV) lamina propria, (V) muscle, and (VI) glass plate. (B) OCT image of mouse tongue; lamin propira (IV) can be identified by brighter contrast. (C) Corresponding dynamic contrast mOCT image with a focus in basal layer (I-V) and even nuclei (*) are visible. (D) Dynamic contrast m OCT image with a focus in the lamina propria; the image size is 380x500 μm (zx); scale bar, 100 μm [from ref. (221)].

Figure 9

Angiographic OCT allows the visualization of elongated capillary loops in the superficial papillary dermis and the underlying vessel plexus. In comparison to the healthy control (A), changes of vascular pattern, vessel diameter, depth, and density can be observed in lesional skin in atopic dermatitis (B) and in plaque psoriasis (C).

Figure 8

Acute and chronic inflammatory skin diseases can lead to an increase of the epidermal layer. Compared to healthy skin (A), involved skin in atopic dermatitis (B) and in plaque psoriasis (C) exhibit a thicker epidermal layer. Changes of epidermal thickness (green line) can be visualized in vertical B-scans and measured by OCT.