Monthly Archives: December 2019

Preclinical MRI

Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful tools in modern science. Since its discovery 50 years ago, in 1945, it has spread from physics to chemistry, biosciences, material research and medical diagnosis.NMR spectroscopy uses the magnetic property, called spin, of a nucleus in an atom. When a sample is set in a strong magnetic field, it is possible to transfer energy into the spin system in the form of radiofrequency pulses and change the state of the system. After the pulse, the system relaxes back to its state of equilibrium, sending a weak signal that can be recorded. Because every nuclear spin in a molecule senses also the small magnetic fields of its nearest neighbours, it is possible to separate the signals coming from different atomic surroundings. The structure of the molecule can be determined from these individual signals.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.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.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 �m and even 25 �m 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.