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Preclinical Imaging: an Essential Ally in Modern Biosciences

Preclinical Imaging: an Essential Ally in Modern Biosciences

 

Last month, in October a new review article titled Preclinical Imaging: an Essential Ally in Modern Biosciences on preclinical imaging technologies was published in the Molecular Diagnosis & Therapy journal. The journal provides insights into the latest molecular diagnostic and pharmacogenomic techniques and their use in personalized medicine.

Cunha, Lídia, Ildiko Horvath, Sara Ferreira, Joana Lemos, Pedro Costa, Domingos Vieira, Dániel S. Veres, et al. 2013. “Preclinical Imaging: An Essential Ally in Modern Biosciences.” Molecular Diagnosis & Therapy: 1–21. doi:10.1007/s40291-013-0062-3.

The find out that actually what is small-animal or preclinical imaging, P. Zanzonico from MSKCC has provided a good definition, stating that 'it constitutes a way of assessing biological structures and function in vivo by noninvasive means, allowing the collection of quantitative information, both in health and disease states' [1]. 

The main role of preclinical imaging is to deliver translational answers for serious health-related problems of the growing and aging world population. Small animal models have to represent a bridge between discoveries at the molecular level and clinical implementation in diagnostics or therapeutics. Small animal imaging is being used in a wide variety of lines of research, especially in infection, inflammation, oncology, cardiology, and neurosciences.

The article summarizes the general properties of diagnostic imaging modalities and reviews them one-by-one including Positron emission tomography (PET), Single photon emission computed tomography (SPECT), Optical imaging (OI), Computed tomography (CT), Magnetic resonance imaging (MRI) and Ultrasound (US) and their related  instrumentation of these modalities in small animal imaging. A separate and well detailed section is dedicated to the comparison of micro-SPECT and micro-PET. The general parameters are summarized in a large table listing imaging characteristics (spatial resolution, sensitivity, penetration depth, temporal resolution), related costs, probe types, major advantages, disadvantages and their application areas.  

There are inherent limitations to each imaging modality - this has brought commercial multi-modality systems 10+ years ago to the market.  Multimodal combination has enabled some of the most important limitations of each imaging modality to be overcome when used alone. The considerations are explained in the tenth sections of the article.
It's an honor to see multi-modality images of PET/MRI and SPECT/MRI acquired by our nanoScan imagers in the article.

A SPECT/MRI application was selected as the image of this blog post. The image shows transverse slices of SPECT and MRI images of a mouse brain. SPECT was acquired using a specific agent for cortical benzodiazepine receptors (123I-NNC13-82431). The lack of anatomical information of SPECT acquisition is complemented with the information provided by MRI, in which the eyes, the olfactory bulbs and the first and second ventricles are shown. The multimodality SPECT/MRI image provides information about functional benzodiazepine receptors from SPECT allied to good soft tissue contrast from the MRI.

Abstract of the Article

Translational research is changing the practice of modern medicine and the way in which health problems are approached and solved. The use of small-animal models in basic and preclinical sciences is a major keystone for these kinds of research and development strategies, representing a bridge between discoveries at the molecular level and clinical implementation in diagnostics and/or therapeutics. The development of high-resolution in vivo imaging technologies provides a unique opportunity for studying disease in real time, in a quantitative way, at the molecular level, along with the ability to repeatedly and non-invasively monitor disease progression or response to treatment. The greatest advantages of preclinical imaging techniques include the reduction of biological variability and the opportunity to acquire, in continuity, an impressive amount of unique information (without interfering with the biological process under study) in distinct forms, repeated or modulated as needed, along with the substantial reduction in the number of animals required for a particular study, fully complying with 3R (Replacement, Reduction and Refinement) policies. The most suitable modalities for small-animal in vivo imaging applications are based on nuclear medicine techniques (essentially, positron emission tomography [PET] and single photon emission computed tomography [SPECT]), optical imaging (OI), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy imaging (MRSI), and ultrasound. Each modality has intrinsic advantages and limitations. More recently, aiming to overcome the inherent limitations of each imaging modality, multimodality devices designed to provide complementary information upon the pathophysiological process under study have gained popularity. The combination of high-resolution modalities, like micro-CT or micro-MRI, with highly sensitive techniques providing functional information, such as micro-PET or micro-SPECT, will continue to broaden the horizons of research in such key areas as infection, oncology, cardiology, and neurology, contributing not only to the understanding of the underlying mechanisms of disease, but also providing efficient and unique tools for evaluating new chemical entities and candidate drugs. The added value of small-animal imaging techniques has driven their increasing use by pharmaceutical companies, contract research organizations, and research institutions.

[1] Zanzonico P. Noninvasive imaging for supporting basic research. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 3–16. (Springer; Google Books)

 

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GenEngNews: Raising the Bar in Preclinical Imaging

GenEngNews: Raising the Bar in Preclinical Imaging

Back in May 2013, I gave a talk titled "The Motivations and Systems for High Content In-vivo Tomographic Imaging in
Drug Discovery" at the 6th Imaging in Drug Discovery & Development Conference in Boston. Mediso USA was the Silver Sponsor for the event.

According to GTC this is "the only imaging conference that brings together high-level/influential leaders with decision-making authority from the pharmaceutical industry, academia, and government to share their knowledge and expertise in drug discovery and development". Needles to say, the sessions were indeed interesting, with an interesting mix from academia, government, pharma and imaging companies.

Session topics included:

  1. Advantages and Challenges of Available Imaging Modalities
  2. Translational Imaging Applications: Preclinical to Clinical
  3. Imaging Applications Across Multiple Therapeutic Areas
  4. Molecular Imaging and Diagnostic Approaches and Capabilities
  5. High Content Imaging, Quantitative Imaging and Modeling Capabilities

The November issue of the was published today in the Genetic Engineering & Biotechnology News, with the Feature Article: Raising the Bar in Preclinical Imaging written by MaryAnn Labant. The article is based on presentations given at the May GTC Imaging in Drug Discovery and Development Conference.

Please find below our related section from the second page of the online article.

Integrated Imaging Systems

Preclinical PET scanners with an integrated microCT have substantially improved the anatomical registration of PET predominately to the skeleton, yet little progress has been made in soft tissue contrast, even with the use of a CT contrast agent.

nanoScan PET-MRIIntegrated PET/MRI or SPECT/MRI systems offer many benefits. MRI uses no radiation, offers better soft tissue contrast, and provides molecular readouts. To date, preclinical PET imaging combined with MRI has been performed using two independent systems and a bespoke co-registration algorithm to fuse the images.

Mediso recently commercialized the first serially produced, fully integrated, automated PET/MRI system, the nanoScan PET/MRI, and a fully integrated, automated SPECT/MRI system, the nanoScan SPECT/MRI. Single systems enable use of the same imaging technology, imaging protocol, and biomarkers for small to large subjects.

According to Illes J. Muller, managing partner, preclinical PET/MRI and SPECT/MRI allow combination of radionuclide biomarkers with an MRI contrast agent on a routine basis, an attractive prospect for evaluating new drugs for oncology, neurology, and cardiovascular disease. Now, physiological/metabolic readouts can be combined with high-resolution, soft-tissue contrast as well as dynamic functional perfusion imaging.

nanoscan SPECT-MRIIn addition, SPECT provides the ability to perform multi-isotope imaging, probing two or more molecular pathways simultaneously by detecting isotopes with different emission energies, and has no physical limits in resolution. SPECT/MRI technology is less expensive. The labeling is easier, and no on-site cyclotron is required.

A potential major application for multimodal emission tomography combined with MRI is quantitative 3D imaging of tumor heterogeneity. To assess the spatial distribution of a given PET or SPECT biomarker within a tumor requires ultra-high resolution and high sensitivity and corrections for tumor perfusion. MRI is able to differentiate between healthy and dead tumor tissue for tumor response evaluation.

Note: This was the related section from the article, with links added to the relevant pages of Mediso USA website.

Blog Image

The blog image shows a Mouse Tumor Heterogeneity Study performed with nanoScan PET/MRI. The mouse was injected with 3 MBq Ga68-DOTA-TATE and imaged for 15 minutes at 60-75 min post injection.

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