Preclinical imaging: The use of preclinical MRI for characterization of disease progression and response to therapy

written by: Uri Rapoprt; article published: year 2010, month 05;

In: Root » Education and reference » Science and research

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Preclinical imaging is the visualization of animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. Imaging modalities that are non-invasive and in vivo have become especially important to study animal models longitudinally. Broadly speaking, these imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques.

Magnetic Resonance Imaging (MRI)

MRI or Magnetic Resonance Imaging is a scanning method developed primarily for use in medicine to provide doctors with the ability to view all sorts of body structures and organs including soft tissues. MRI is arguably the greatest advance in diagnostic medical techniques over the past century.

MRI is a diagnostic procedure that utilizes magnetic and radio waves to produce detailed images of the body's structures (including soft tissues), without the use of X-rays or other form of radiation.

Magnetic Resonance Imaging (MRI) exploits the nuclear magnetic alignments of different atoms inside a magnetic field to generate images. An MRI machine consists of large magnets that generate magnetic fields around the target of analysis. These magnetic fields cause paramagnetic atoms such as hydrogen, gadolinium, and manganese to align themselves in a magnetic dipole along the magnetic fields, created by the radiofrequency (RF) coils inside the MRI machine. What the machine captures from the subject is the relaxation of the atoms as they return to their normal alignment when the RF pulse is temporarily ceased. With this data, a computer will generate an image of the subject based on the resonance characteristics of different tissue types.

Preclinical MRI

Magnetic resonance imaging (MRI) has been widely used in preclinical research on experimental small animals.

Studies have typically been aimed at understanding the patophysiological status and evaluating the efficacy/side effects of newly developed treatments such as pharmaceutical and regenerative medicine.

Although small animal scanners are superior to clinical scanners in terms of providing a better signal-to-noise ratio, the available pulse sequences are different from those in clinical scanners, and the magnetic field strength is often much higher.

Small animal magnetic resonance imaging (MRI) techniques are currently one of the premier research tools available to probe and validate structural and functional relationships at the biosystem, cellular or molecular level. In fact, a growing number of MRI facilities dedicated to imaging small animal models of disease now exist in a variety of environments encompassing pharmaceutical, medical and basic science research. Preclinical Imaging studies are typically performed at high magnetic field strengths, yielding high signal-to-noise ratios (SNRs) and soft tissue contrast compared to other available modalities.

Preclinical MRI applications.

The range of preclinical MRI applications includes brain and organ imaging, tumor assessment, disease progression and functional imaging. Other potential research applications include investigation of new contrast mechanisms and agents, monitoring gene expression, analysis of protein interactions, and determination of pharmacokinetics.

A majority of preclinical studies, especially those that involve characterization of disease progression and response to therapy in transgenic animal models, require an elaborate experimental design using large cohorts of animals. The acquisition of these large MRI data sets can be expensive, time consuming and labor intensive. Therefore, automation techniques to improve throughput, increase efficiency and/or improve accuracy would represent a significant advance, especially with regard to screening and phenotyping animals.

Advantages of pre-clinical MRI:

Good spatial resolution, up to 100 µm and even 25 µm in very high strength magnetic fields.

Has excellent contrast resolution to distinguish between normal and pathological tissue.

Preclinical-MRI can be used in a wide variety of applications, including anatomical, functional, and molecular imaging.

Safety: since micro-MRI's mechanism is based on a magnetic field, it is much safer compared to radiation based imaging modalities such as micro-CT and micro-PET.

Weaknesses:

One of the biggest drawbacks of micro-MRI is its cost. Depending on the magnetic strength (which determines resolution), systems used for animal imaging between 1.5 and 14 teslas in magnetic flux density range from $1 million to over $6 million, with most systems costing around $2 million.

Extremely long image acquisition time, spanning into minutes and even hours. This may negatively affect animals that are anesthetized for long periods of time.

In addition, micro-MRI typically captures a snapshot of the subject in time, and thus it is unable to study blood flow and other real-time processes well. Even with recent advances in high strength functional micro-MRI, there is still around a 10-15 second lag time to reach peak signal intensity, making important information such as blood flow velocity quantification difficult to access.

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