Synopsis
Combining metabolic imaging methods with spectroscopy methods allows for the appreciation of spatial patterns of physiology and metabolism and the complexities of normal and pathological physiology. A variety of approaches, including traditional spectroscopy, metabolic mapping, and indirect detection of metabolites, are available.Highlights
1. Traditional spectroscopy approaches are often based on observation of 31P, 13C, and 1H nuclei. These permit the investigation of many basic and translational and clinical physiology questions.
2. Building on this, approaches using metabolic mapping allow the appreciation of spatial patterns of metabolism. These have been integrated imaging approaches to provide additional insights.
3. Recently, new approaches based on the indirect detection of metabolites by way of thir proton exchange with water have been developed.
4. In addition, there are opportunities to integrate MR data with those obtain using other modalities, such as near-infrared spectroscopy and PET.
Target Audience
Researchers and clinical practitioners who are interested in
non-invasive or minimally invasive capabilities for characterizing the
physiological and metabolic characteristics of healthy and diseased organs.
Objectives
After listening to this presentation,
you should be able to:
1. Describe the rationale for joint spectroscopic-imaging characterization of healthy or diseased organs;
2. Describe
magnetic resonance imaging and spectroscopy approaches available for
physiologic and metabolic characterization of healthy and diseased organs;
3. List one or two
potential applications of these methods to biomedical problems of interest.
Rationale for Metabolic Imaging with Spectroscopy
Understanding how organs and
organ systems function is a fundamental aspect of biomedical science. These
properties are of interest not just to studies of basic biomedical sciences,
but also to studies of diseases and how they alter function. Metabolic imaging
and spectroscopy methods allow us to quantify selected physiologic and metabolic properties
of organs and organ systems. Their non-invasive or minimally invasive nature makes
it possible to study these functions while perturbing the system only
minimally.
Physiological systems are
highly complex. There are interesting and complex relationships between an
organ’s structure and many aspects of its function. Typically, these many
aspects of function are inter-related, such that any single function cannot be
fully understood without knowing the larger context. Thus, it is unlikely that any single measurement
would be able to fully characterize all of the salient aspects of a physiologic
system. This indicates the value of using multi-model approaches.
Finally, many diseases
present with a spatially heterogeneous pathology. Techniques such as MRI, which
are based on tomographic imaging in two or three dimensions, allow us to
recognize and characterize this heterogeneity.
Approaches
to Metabolic Imaging with Spectroscopy with Applications to Biomedical Sciences
Approaches based on traditional spectroscopy methods
In
vivo MR spectroscopy
studies have most often been based on observation of 31P, 13C, and 1H nuclei. 31P
MRS methods have been used for nearly 40 years to study the energetic
properties of muscle contraction [1], including advancing the understanding
of issues such as the control of flux through metabolic reactions [2-4], neuromuscular disorders [5], and skeletal muscle fatigue [6]. 13C methods, typically incorporating
1H decoupling methods, have been used for applications such as quantifying
glycogen levels [7] or to study flux through metabolic
pathways [8]. These methods have found considerable
application in metabolic diseases such as type 2 diabetes mellitus or other
insulin-resistant conditions [9-12]. The other major form of in vivo spectroscopy is based on observing 1H resonances. Applications
have included carnosine-based pH measurements during and after exercise [13, 14], intramyocellular lipids, editing of lactate and other
small metabolites to study basic aspects of function [14], or neurotransmitter concentrations and
their cycles [15, 16]. Because in most cases the capabilities of 31P, 13C, and 1H
methods do not overlap, it is desirable to combine several of these methods to
gain an integrated view of a physiologic problem [17, 18].
Traditional MR spectroscopy
methods often use a surface coil to acquire a signal from a region of the body.
In this case, localization is based only on the limited excitation volume of
the coil and the placement of the coil near the body region of interest. Signals
are received from a volume defined by the radius of the coil, and are strongest
from the tissue directly under the coil. Several approaches are available to
allow the appreciation of spatial heterogeneity. Localized spectroscopy methods
use gradients and selective RF pulses to localize signals to a deep region of
tissue, so that signals are observed only from the tissue of interest. Methods
such as chemical shift imaging [19] allow the formation of metabolic maps
based on the acquisition of phase-encoded spectra across a large volume of
tissue. Metabolic mapping is also possible by suppressing all metabolite signals
through either 1H editing sequences [20] or based on long-echo time suppression of
short T2 species [21]. Metabolic mapping has been integrated
with traditional physiologic imaging methods to gain a more complete view of
conditions such as muscle exercise [22].
Approaches based on indirect detection
Recently, a new class of
metabolic imaging methods, based on the indirect detection of metabolites, has emerged.
These methods are based on the chemical exchange of protons between small
metabolites or proteins and water and take advantage of conventional saturation-transfer
methods [23]. Certain of these exchange rates, such as
those between the base-catalyzed exchange between amide protons and water [24-26], are pH-sensitive; this has fostered
applications such as pH imaging. Other applications
of chemical exchange saturation transfer methods include the indirect detection
of glycogen [27, 28] and small metabolites [29]. These sequences offer advantages of
relatively higher signal-to-noise ratios and the lack of need for specialized
equipment, but the signals depend on many factors, including the T1s, relatively pool sizes, and
exchange rates. This has made quantitation challenging.
Integration with other imaging and spectroscopy modalities
Finally, it should be noted that the possibilities for integrating multiple non-invasive methods are not limited to MR. For example, MR imaging has been integrated with near-infrared
spectroscopy to gain insight into the mechanisms of the BOLD response in muscle [30, 31] and brain [32]; and the emerging methodology of PET-MR will
afford a considerable array of new opportunities to combine physiological and
biochemical information.
Acknowledgements
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