WE‐H‐206‐00: Advances in Preclinical Imaging
Authors: La Riviere Patrick 
Published: July 2016

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy.

Learning Objectives:
To understand the contrast mechanism of PAT
To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals.

Learning Objectives:
To learn about the two major multi‐modality molecular imaging techniques of small animals.
To learn about the spatial resolution achievable by the molecular imaging systems for small animal today.
To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging.

Learning Objectives:
To learn the basic principles of XRF/XFCT imaging
To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198