Example of approaches to brain stress testing: bold magnetic resonance with computer-controlled research proposal

Introduction

Human brain is a complex organ and so are its diseases. Over the years numerous techniques, devices and processes have been developed that can help us to correctly access and diagnose the problem areas and provide solutions to them (14). Computer controlled delivery of carbon dioxide is a method that is conducted with the help of a gas blender that works to supply and alter carbon dioxide to the brain creating tensions in the brain (10) (16).

Carbon dioxide challenge

Changes in the carbon dioxide tensions in the brain are capable of sufficiently affecting the Brain and its functioning (1) . Due to increased carbon dioxide level in the Cerebral blood flow (CBF) can shoot up to a considerable degree of 5-11 percent/mmHg along with the rise in cerebral blood volume (7) (11). When the CO2 challenge is taken along with magnetic resonance imaging (MRI), the improvements in the reproducibility and precision the true and exact regional assessment can be optimally depicted (7). To determine the changes in the cerebral blood flow (CBR) and tissue oxygenation, it has been observed that the higher field strength magnetic resonance imaging using blood oxygen level dependent (BOLD) contrast provides better and improved resolution (8) (5). Most researchers use BOLD (Blood oxygen level dependent) method for finding and locating the most active parts of the brain (9). Functional Magnetic Resonance Imaging, fMRI
Functional Magnetic Resonance Imaging, fMRI is the method to investigate the brain areas and understand the active human brain. Functional Magnetic Resonance Imaging, fMRI studies always analyse the effects due to the diseases at the group level and not the individual level (17) (4). FMRI is a kind of brain stress test that is used to determine the brain response to the given challenges (3). The aim is to look at the pattern of activation and not at the absolute value of the BOLD change (18) (12).

Diagnosis and treatment

The two studies, namely the resting state and default mode are used to define the consciousness of the brain and the BOLD imaging that is directly related to the tasks. It is then used to demonstrate brain’s regional interconnectivity (8). Transcranial Doppler is a technique which is used to periodically access the blood velocity alterations that occur after the CO2 challenge (7). ). The brain signals are always based on quantitative measures, so determining the neural activities within the brain is done by BOLD (12).
Higher levels of carbon dioxide raise the intracranial volume and pressure thus demanding greater neurocritical and neuroanesthesia care to control the amount of arterial CO2 (13). Such alterations in the amount of CO2 or CO2 challenge and cerebral blood flow take place due to the incidents of brain injury or diseases (19) (20).

Proposed project

In the proposed project functional magnetic resonance imaging has been introduced. However, due to the intrinsic complexity of the signal based on the opposing ways of alterations in blood vascular flow and oxygen metabolism and the interference of certain technical glitches of the image acquisition method the BOLD-fMri method alone stands as an unreliable test. In order to correctly benefit from this technique it is essential to gather the BOLD data as well as CMRO2 i. e. the oxygen metabolism changes. In other words to deal with the issue, it is necessary to additionally take into consideration the oxygen metabolism (CMRO2) measurements. In several studies, it has been found that the coupling ratio of cerebral blood flow (CBF) to the oxygen metabolism (CMRO2) changes had a greater degree of reproducibility as compared to the individual responses.

Benefits of proposed study

As it has been pointed out earlier with the advanced system of taking into consideration the BOLD data and CMRO2 degree of reproducibility can be achieved. It advances the study of the working human brain and provides more in depth insights into the underlying issues and requirements that can then be addressed accordingly (12).

Research plan

The stepwise change and the ramp change are the two patterns of bringing alterations in CO2. Stepwise change is used to study the dynamics of the vascular response. While ramp change helps to understand the steady-state response to carbon dioxide (2). Stepwise change is brought about by the square wave stimulus and ramp stimulus generates ramp changes. Dynamic brain imaging in an atmosphere of carefully controlled changes in carbon dioxide is used to understand cerebrovascular reactivity (CVR).

The two methods used for analysis of the stimulus obtained from the studies are as follows.

– The ratio between the mean BOLD signals to the alterations in carbon dioxide to gauge regional cerebrovascular reactivity (CVR) gives the output as a voxel-based ratio of change, MR-BOLD (2).
– Detrended fluctuation analysis (DFA) can be used to determine the voxel-based fractal time analysis of the MRI BOLD signal. This method can be used to identify the activated cortical areas (2) (6) (15).

Summary

The changes caused to the activeness of the brain areas are detected and mapped. This process is called Magnetic Resonance Imaging (MRI). MRI images the areas of brain based on the blood oxygen level dependent (BOLD) approach. This technique is used to conduct the brain stress testing to detect the active brain areas. In brain stress testing, the patient is given this challenge and the physiological responses in the brain are measured quantitatively to ascertain the working of the brain. The challenge given to the patient can be of the form of some chosen task or stimulus or a change of state due to a drug or other physiological manipulation.
Since the above mentioned techniques provide a specialized method to deal with the complexities of the human brain, the dual stimulus of square wave and ramp and the dual analysis carried out can to a great extent provide true assessment of the working brain.

References

1. Battisti-Charbonney A, Fisher JA, Duffin J (2011) Cerebrovascular and cardiovascular
responses to isocapnic hypoxia. Resp Physiol Neurobiol 179: 259–268.
2. Buxton, R. B. (n. d.). The Brain Stress Test. San Diego, USA: Department of Radiology, University of California.
3. Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic
resonance neuroimages. Computers Biomed Res 29: 162–173.
4. Goode SD, Krishan S, Alexakis C, Mahajan R, Auer DP (2009) Precision of
cerebrovascular reactivity assessment with use of different quantification methods for hypercapnia functional MR imaging. Am J Neuroradiol 30: 972–977.
5. Heyn C, Poublanc J, Crawley A, Mandell D, Han JS, et al. (2010) Quantification of
cerebrovascular reactivity by blood oxygen level-dependent MR imaging and correlation with conventional angiography in patients with Moyamoya disease. Am J Neuroradiol 31: 862–867.
6. Hu J, Lee JM, Gao J, White KD, Crosson B (2008) Assessing a signal model and
identifying brain activity from fMRI data by a detrending-based fractal analysis. Brain Struct Funct 212: 417–426.
7. Mandell, D. M., & Mutch, W. A. (2012, November). Approaches to Brain Stress Testing: BOLD Magnetic. PLOS one.
8. Mutch, W. A., et al., Approaches to brain stress testing: BOLD magnetic resonance
imaging with computer-controlled delivery of carbon dioxide. PLoS One, 2012. 7(11): p. e47443.
9. Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood
106(6): 1901-10.
10. Lawall H, Bramlage P, Amann B (2011) Treatment of peripheral arterial disease using
stem and progenitor cell therapy Journal of Vascular Surgery 53(2): 445-53.
11. Lee KH, Byun SS, Paik JY, Lee SY, Song SH, Choe YS, Kim BT (2003) Cell uptake and
tissue distribution of radioiodine labelled D-luciferin: implications for luciferase based gene imaging. Nuclear Medicine Communications 24(9): 1003-9.
12. Leontiev, O. and R. B. Buxton, Reproducibility of BOLD, perfusion, and CMRO(2)
measurements with calibrated-BOLD fMRI. Neuroimage, 2007. 35(1): p. 175-84.
13. Noth, U., et al., Mapping of the cerebral vascular response to hypoxia and hypercapnia
using quantitative perfusion MRI at 3 T. NMR Biomed, 2008. 21(5): p. 464-72.
14. Pillai, J. J., & Zaca, D. (2011). Clinical utility of cerebrovascular reactivity mapping in patients. World J Clin Oncol,, pp. 397-403.
15. Pindzola RR, Sashin D, Nemoto EM, Kuwabara H, Wilson JW, et al. (2006) Identifying
regions of compromised hemodynamics in symptomatic carotid occlusion by cerebrovascular reactivity and oxygen extraction fraction. Neurol Res 28: 149–154.
16. Regensteiner JG, Hiatt WR, Coll JR, Criqui MH, Treat-Jacobson D, McDermott MM,
Hirsch AT (2008) The impact of peripheral arterial disease on health-related quality of life in the Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) Program Vascular Medicine 13(1): 15-24.
17. Simon, A. B., et al., A novel method of combining blood oxygenation and blood flow
sensitive magnetic resonance imaging techniques to measure the cerebral blood flow
and oxygen metabolism responses to an unknown neural stimulus. PLoS One, 2013.
8(1): p. e54816.
18. Slessarev M, Han J, Mardimae A, Prisman E, Preiss D, et al. (2007) Prospective targeting
and control of end-tidal CO2 and O2 concentrations. J Physiol 581: 1207–1219.
19. Yonas H, Pindzola RR (1994) Physiological determination of cerebrovascular reserves
and its use in clinical management. Cerebrovasc Brain Metab Rev 6: 325–340.
20. Ziadloo A, Burks S, Gold E, Chaudhry A, Merino M, Frenkel V, Frank J (in press)
Enhanced homing permeability and retention of bone marrow stromal cells (BMSC) by non-invasive pulsed focused ultrasound. Stem Cells.