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==Team== *[[Bryn Martin]] *[[Eleonora Fonari]] *[[John Oshinski]] *[[Raphael Heinzer]] ==The problem== Craniospinal compliance has been thought to be an important indicator of craniospinal health. Some have postulated that, when properly functioning, the spinal subarachnoid space (SAS) compliance may act as a notch filter to dampen out cerebrospinal (CSF) flow pulsations (Madsen, Egnor et al. 2006; Luciano and Dombrowski 2007). However, a non-invasive technique for assessment of craniospinal compliance has not been validated. The proposed study aims to investigate the sensitivity of a novel non-invasive MR technique to changes in intracranial pressure (ICP), which is directly related with craniospinal compliance. Communication between the intrathorasic and ICP due to postural changes (Dabrowski 2007; De Keulenaer, Cheatham et al. 2009), coughing (Sansur, Heiss et al. 2003), valsalva and Queckenstedt’s test, and abdominal pressure (Bloomfield, Ridings et al. 1997) has been well documented (Williams 1981; Williams 1981; Heiss, Patronas et al. 1999; Sansur, Heiss et al. 2003). These pressure changes are transmitted from the abdomen into the CSF system (ICP) through the dural venous sinuses and epidural venous plexus (Figure 1 and Figure 2). Thus, it is possible to vary ICP and compliance by a number of non-invasive tests. The changes in ICP are expected to be detectable by spinal CSF velocity wave speed, since the spinal canal forms a compliant tube-like system which transmits cranial CSF pulsations through the spinal SAS (~1 cc per cardiac cycle at C2 level (Loth, Yardimci et al. 2001; Martin, Kalata et al. 2005)). ==Hypothesis and research objectives== We hypothesize that the spinal CSF velocity wave speed is indicative of ICP which can be modified non-invasively by a series of tests. The goal of this research is thus to validate the sensitivity of a novel MR protocol to changes in ICP. ==Methods and study outline== ;A. in vivo MR measurements. Our approach is to obtain CSF velocity wave speed measurements using the technique described by Kalata et al. (Kalata, Martin et al. 2009) on healthy male 20-30 year old subjects under two conditions. #Baseline MR CSF velocity wave speed measurements (Kalata, Martin et al. 2009) will be obtained on the subject at normal pressure in the supine position. #A series of three tests will be performed on the subject while obtaining identical MR measurements as the baseline measurement. The three tests will include continuous positive airway pressure (CPAP) (Bowie, O'Connor et al. 2001), Queckenstedt’s test (Williams 1981; Williams 1981; Heiss, Patronas et al. 1999; Sansur, Heiss et al. 2003), and placement of a mass on the stomach. The CPAP and Queckenstedt’s test will be performed at moderately elevated pressures (i.e. ~15 cm H2O). A mass will be placed on the stomach (i.e. 10 Kg water bags). The subject’s heart rate, Oxygen saturation (SpO2), and transcutaneous carbon dioxide tension (PCO2) will be monitored. Subjects will be able to discontinue testing at any time. A medical doctor will be present throughout the duration of testing. #The baseline measurement and all three tests will initially be conducted on three subjects to determine which are best suited to change CSF velocity wave speed in the spinal subarachnoid space. Subsequent tests will be performed using the most promising tests. ;B. Single-blind processing of MR data. CSF velocity wave speed in the spinal canal for each subject will be obtained from the MR study data using the technique employed by Kalata et al. (Kalata, Martin et al. 2009) and Filden et al. (Fielden, Fornwalt et al. 2008). These calculations will be performed by an engineer blinded to the test case. ==Expected results and potential impact== The proposed work will determine if the non-invasive MR test is sensitive to changes in ICP caused by a series of tests. If proven efficacious, it could be further explored to understand its sensitivity and accuracy, and could have the potential to provide a clinically useful tool for assessment of craniospinal compliance. ==Preliminary results== ==References== Bergel, D. H. (1961). "The static elastic properties of the arterial wall." J Physiol 156(3): 445-57. Bloomfield, G. L., P. C. Ridings, et al. (1997). "A proposed relationship between increased intra-abdominal, intrathoracic, and intracranial pressure." Crit Care Med 25(3): 496-503. Bowie, R. A., P. J. O'Connor, et al. (2001). "The effect of continuous positive airway pressure on cerebral blood flow velocity in awake volunteers." Anesth Analg 92(2): 415-7. Dabrowski, W. (2007). "Changes in intra-abdominal pressure and central venous and brain venous blood pressure in patients during extracorporeal circulation." Med Sci Monit 13(12): CR548-54. Dawson, D. L. (2003). "Cardiovascular haemodynamics and Doppler waveforms explained, 1st edition (vol 16, pg 805, 2002)." Annals of Vascular Surgery 17(3): 347-347. De Keulenaer, B. L., M. L. Cheatham, et al. (2009). "Intra-abdominal pressure measurements in lateral decubitus versus supine position." Acta Clin Belg 64(3): 210-5. Fielden, S. W., B. K. Fornwalt, et al. (2008). "A new method for the determination of aortic pulse wave velocity using cross-correlation on 2D PCMR velocity data." J Magn Reson Imaging 27(6): 1382-7. Hayashi, K., H. Handa, et al. (1980). "Stiffness and elastic behavior of human intracranial and extracranial arteries." J Biomech 13(2): 175-84. Heiss, J. D., N. Patronas, et al. (1999). "Elucidating the pathophysiology of syringomyelia." J Neurosurg 91(4): 553-62. Kalata, W., B. A. Martin, et al. (2009). "MR Measurement of Cerebrospinal Fluid Velocity Wave Speed in the Spinal Canal." IEEE Transactions on Biomedical Engineering. Kalata, W., B. A. Martin, et al. (2009). "MR measurement of cerebrospinal fluid velocity wave speed in the spinal canal." IEEE Trans Biomed Eng 56(6): 1765-8. Karahalios, D. G., H. L. Rekate, et al. (1996). "Elevated intracranial venous pressure as a universal mechanism in pseudotumor cerebri of varying etiologies." Neurology 46(1): 198-202. Lockey, P., G. Poots, et al. (1975). "Theoretical aspects of the attenuation of pressure pulses within cerebrospinal-fluid pathways." Med Biol Eng 13(6): 861-9. Loth, F., P. F. Fischer, et al. (2003). "Transitional flow at the venous anastomosis of an arteriovenous graft: potential activation of the ERK1/2 mechanotransduction pathway." J Biomech Eng 125(1): 49-61. Loth, F., M. A. Yardimci, et al. (2001). "Hydrodynamic modeling of cerebrospinal fluid motion within the spinal cavity." J Biomech Eng 123(1): 71-9. Luciano, M. and S. Dombrowski (2007). "Hydrocephalus and the heart: interactions of the first and third circulations." Cleve Clin J Med 74 Suppl 1: S128-31. Madsen, J. R., M. Egnor, et al. (2006). "Cerebrospinal fluid pulsatility and hydrocephalus: the fourth circulation." Clin Neurosurg 53: 48-52. Martin, B. A., W. Kalata, et al. (2005). "Syringomyelia hydrodynamics: an in vitro study based on in vivo measurements." J Biomech Eng 127(7): 1110-20. Montolivo, M., E. Bruzzone, et al. (1987). "[Changes in central venous pressure and intracranial pressure following the introduction of positive end-expiratory pressure ventilation in supine and seated position during neurosurgery]." Minerva Anestesiol 53(5): 267-71. Sansur, C. A., J. D. Heiss, et al. (2003). "Pathophysiology of headache associated with cough in patients with Chiari I malformation." J Neurosurg 98(3): 453-8. Ursino, M. (1988). "A mathematical study of human intracranial hydrodynamics. Part 1--The cerebrospinal fluid pulse pressure." Ann Biomed Eng 16(4): 379-401. Williams, B. (1981). "Simultaneous cerebral and spinal fluid pressure recordings. 2. Cerebrospinal dissociation with lesions at the foramen magnum." Acta Neurochir (Wien) 59(1-2): 123-42. Williams, B. (1981). "Simultaneous cerebral and spinal fluid pressure recordings. I. Technique, physiology, and normal results." Acta Neurochir (Wien) 58(3-4): 167-85.

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