Significance of Arterial Spin Labeling in Research and Clinical Studies

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Introduction

The fields of clinical practices and research have been boasted by the inception of MRI as a tool for mapping neuronal activity. The technology is safe and flexible with superb temporal and resolution of its kind. Researches based on functional Magnetic Resolution Imaging (fMRI) depend on Blood Oxygenation Level-Dependent also referred to as BOLD. However, “BOLD has limitations including considerable variability in the BOLD signal between subjects and low-frequency drifts in the MR signal with time, thus BOLD studies are generally restricted to activation paradigms that can be performed in a cyclical on/off pattern.” (1).

The above features present BOLD as an inferior mapping technology for cerebral monitoring. (2). The low-frequency spectrum debacle has been solved with the development of Arterial Spin Labeling (ASL) that shows an even distribution of frequency spectrum; hence, ideal for studying brain functions. The main application of ASL is in the monitoring of cerebral changes brought about by tonic pain. “MRI technology will continue to evolve following its continued use in clinical practices and this necessitates continued researches to further advance MRI concepts.” (3). Therefore, this essay comprehensively covers the revolution and future evolution of ASL as a frontier in clinical practices and research.

Before the inception of ASL, Cerebral Blood Flow (CBF) was being determined by invasive techniques like Positron Emission Tomography (PET). PET technique mainly depended on the use of exogenous agents in contrast imaging. According to (4), “In this technique, researchers inject a radiotracer (which was essentially radioactively labeled water) into the participants.” ASL also applies the use of contrast agents; the only difference is that ASL does not use injections; making it a completely non-invasive process. ASL uses magnetically excited water instead of the radio-activated water used in PET.

In addition, the physical configuration does not play part in image contrast. “Spin-labeling pulse consists typically of a labeling section, during which an RF pulse is applied to the spins upstream of the imaging slice.” (5). The development of new clinical practices like perfusion measurements has become fundamental in a number of neurological protocols. Based on 3T scanning sequences, ASL seems to provide important imaging in monitoring Cerebral Blood Flow (CBF). Contrast image generation technique is based on the speed at which transient MR signals are crumbling away and recorded as relaxation time; T2 and echo time; TE. “Recently clinical research findings have been published using ultra-short echo time (UTE) sequences where TE has been reduced from its typical range of 1-10 milliseconds down to 10-50 microseconds.” (6). Contrasts have created new perspective in imaging as it has made direct imaging of tissues possible. MRI initially had never made imaging of tendons and ligament possible. (7).

ASL Test

Methodology

A group of researchers was given go-ahead from the University Research Ethics Board to embark on testing the viability of ASL technology. It was based on 3T scanning procedures. According to (1):

Prior to imaging, a catheter (size 25 G) was inserted into the flexor muscle in the forearm of the non-dominate hand. An intramuscular infusion of hypertonic (5%) saline was connected. The functional study consists of two parts: a 10-minute resting period, followed by a 20-minute pain period during which hypertonic (5%) saline is continuously infused. Images of cerebral blood flow are acquired throughout the functional study using our ASL technique. During the pain period, the infusion rate was gradually titrated increased to a pain rating of 7 /10 was attained.

Results and Interpretation

A number of observations were made on the two analyses. “Considerable Increases in CBF were observed. The first 5 minutes recorded visible activations; however, the observation was not so in the entire 20 minutes in both the cingulated cortex and anterior. This indicates that the first 5 minutes are in a great way responsible for the entire activation process. Decreasing levels of pain in the later stages of the process explains that there are diminishing effects of cingulated activation; which in turn decreases the level of pain. The experiment illustrates that ASL can monitor changes in CBF brought about by pain stimuli.

This is evidence enough that ASL is a useful concept in the clinical field to analyze the consequences of chronic pain. The findings of this research and its potential are in the clinical practices are significant. However, “Many trade-offs must be made, an understanding of these issues will help the investigators to tailor some of these parameters to specific brain region or study design of interest.” (8).

Examples of ASL Image Techniques and Applications

A number of ASL techniques can be employed to perform perfusion imaging. First, there is Continuous ASL (CASL) which is based on the use of continuous RF pulse. In this process, image slice is placed beneath RF pulse to monitor any magnetic distortions emanating from the RF pulse. However, RF pulse does not carry any blood labeling. The technique can also be referred to as flow-driven inversion. The second technique is called Pulsed ASL (PASL). In this technique, RF pulse is applied on only selected places with inversion of arterial blood. Methods of PASL are generally referred to as spatial inversion and they include: EPISTAR and FAIR.

These techniques produce results that have a number of striking differences with those got through BOLD fMRI. Outcomes obtained via the use of ASL take longer time to produce but have thicker slices than to those of BOLD fMRI. Also, “Changes in perfusion are more localized to the parenchyma, whereas BOLD changes are tied to the veins and venules,” (4). The fundamental difference between the two processes however, lies in the clarity of imaging. Activation signals from ASL are cleaner and clearer than those of BOLD techniques.

The first application of ASL is in the perfusion of trends in acute stroke. According to (9), “Cerebral infarction are primary based upon the use of bipolar crusher gradients to suppress intravascular signal.” Thus, tagging of a patient with a slowed flow may be concealed in the vessel when crusher gradient is applied prior to tissue deposition. In addition, should there be any delay in transition time; there will be a corresponding delay in CBF perfusion detects recorded in the map. Another clinical use of the ASL perfusion mapping technique is in tumor evaluation. Studies indicate that “Tumor grade frequently correlates with various perfusion parameters,” (10).

In this case, a technique referred to as contrast bolus is used to monitor CBV measurements. ASL perfusion mapping for cyst tumor is influenced by time of transit and blood quantity. ASL artificial signals for cyst tumor will be low; however, for a patient who has had surgery, the signals would be large indicating primary neoplasm. It is crucial to distinguish which part of the tumor was monitored when measuring average ASL perfusion.

In high level ASL signals; also knows as hyperperfusion, “Recent studies indicate that most PASL imaging applications with malignant neoplasm, the higher the perfusion of the mass, the higher the histologic grade,” (11). Contrarily, it is important to note that not all hyperperfused masses can be classified as high grade. In medical analysis, the frequently hyperperfused lesions are in meningiomas. A prolonged angiographic blush corresponds to high vascular lesions when contrast administration is applied and as noted by (10), “The enhancing mural nodule neoplasms, such as hemangioblastomas, are some of the most highly perfused lesions we have encountered.”

Conclusion

Since the 1980s, the field of clinical medicine has benefited from ASL technology in terms of applicability in a number of mapping neuronal activities. This has been necessitated by the presence of 3T scanners and future development of the field has been on a steady rise. However, the inception of ASL in the last decade has become an essential tool as a diagnosis means and following its successful testing, and application, future researches in the clinical modalities will vastly depend on the further development of ASL.

References

  1. Clarke, et al. Arterial Spin Labeling functional MRI – a new modality for successfully capturing cerebral blood flow changes associated with tonic pain. Web.
  2. Moonen, C.T.W. and Bandettini, P. A. “Functional MRI.” Medical radiology: Diagnostic imaging. New Jersey: Springer. 2000.
  3. Runge, V.M. et al. The Physics of Clinical MR Taught Through Images. 2nd edn. New York, NY: Thieme. 2008.
  4. University of Michigan. Arterial Spin Labeling (ASL). Web.
  5. Venook, R.D. et al. “Pre-polarized magnetic resonance imaging around metal orthopedic implants.” Magnetic Resonance in Medicine. 2006; 56: 177-186.
  6. Gatehouse, P.D. and Bydder, G.M. “Magnetic resonance imaging of short T-2 components in tissue.” Clinical Radiology. 2003; 58: 1-19.
  7. Robson M.D., Bydder, G.M. “Clinical ultra short echo time imaging of bone and other connective tissues.” NMR in Biomedicine. 2006; 19: 765-780.
  8. Faro, S.H. and Mohamed, F. B. BOLD FMRI: A guide to functional imaging for neuroscientists. Washington, DC: Springer. 2010.
  9. Pollock, J.M, Tan, H., Kraft, R.A, et al. Arterial spin labeled MRI perfusion imaging: Clinical applications. Web.
  10. Noguchi, T., Yoshiura T., Hiwatashi A., et al. Perfusion imaging of brain tumors using arterial spin-labeling: correlation with histopathologic vascular density. AJNR Am J Neuroradiol. 2008; 29:688–693.
  11. Sadowski, E.A., Bennett, L.K., Chan, M.R., et al. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology. 2007; 243:148–157.
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