J Manipulative Physiol Ther. 2014 (Jan); 37 (1): 22–31 ~ FULL TEXT
Jairus J. Quesnele, DC, John J. Triano, DC, PhD,
Michael D. Noseworthy, PhD, Greg D. Wells, PhD
Chiropractor, Private Practice,
Division of Graduate Studies,
Canadian Memorial Chiropractic College,
Toronto, Ontario, Canada
OBJECTIVE: The objective of the study was to investigate the cerebrovascular hemodynamic response of cervical spine positions including rotation and cervical spine manipulation in vivo using magnetic resonance imaging technology on the vertebral artery (VA).
METHODS: This pilot study was conducted as a blinded examiner cohort with 4 randomized clinical tasks. Ten healthy male participants aged 24 to 30 years (mean, 26.8 years) volunteered to participate in the study. None of the participants had a history of disabling neck, arm, or headache pain within the last 6 months. They did not have any current or history of neurologic symptoms. In a neutral head position, physiologic measures of VA blood flow and velocity at the C1-2 spinal level were obtained using phase-contrast magnetic resonance imaging after 3 different head positions and a chiropractic upper cervical spinal manipulation. A total of 30 flow-encoded phase-contrast images were collected over the cardiac cycle, in each of the 4 conditions, and were used to provide a blood flow profile for one complete cardiac cycle. Differences between flow (in milliliters per second) and velocity (in centimeters per second) variables were evaluated using repeated-measures analysis of variance.
RESULTS: The side-to-side difference between ipsilateral and contralateral VA velocities was not significant for either velocities (P = .14) or flows (P = .19) throughout the conditions. There were no other interactions or trends toward a difference for any of the other blood flow or velocity variables.
CONCLUSIONS: There were no significant changes in blood flow or velocity in the vertebral arteries of healthy young male adults after various head positions and cervical spine manipulations.
From the Full-Text Article:
Each year, stroke costs the Canadian economy $3.6 billion in physician services, hospital costs, lost wages, and decreased productivity.  Although rare in the general population, vertebrobasilar artery (VBA) stroke, such as spontaneous vertebral artery (VA) dissection, is a leading cause of nonatherosclerotic stroke in young adults. [2–4] It has been proposed that an underlying genetic predisposition, triggered by risk factors associated with environmental exposure, with or without trivial trauma may serve as an etiologic model.  However, the exact pathogenesis of VBA stroke is poorly understood. [4, 6] It is well documented that patients who experience VBA stroke have a change in blood flow in the affected VA. [2, 7, 8] Others have noted signs and symptoms of vertebrobasilar insufficiency with certain head positions. [9–12] Authors speculate that mechanical compression or stretching of the VA at extremes of head position is a potential causative factor for VA blood flow change and is most likely to occur in the suboccipital part (V3) of the VA. [13–17] As a result of Bernoulli principle, there is an increase in blood flow velocity at and/or immediately beyond the point of constriction of a vessel owing to either stretching or compressive forces.  This may result in spurting and turbulent flow immediately downstream from the region of distortion  that may evoke a local thrombogenic response,  leading to VBA stroke. A change in VA blood flow after head rotation, especially contralateral to the direction of rotation, has been demonstrated in several studies.  However, these results yield some inconsistencies and are inconclusive with respect to clinical relevancy. [14, 15, 17]
There is continuing controversy about the effects of cervical range of motion and therapeutic physical interventions, including cervical spinal manipulation (CSM) and or sustained mobilizations, on the blood flow within the VAs and cerebrum. End-of-range motion, manipulation, and mobilization techniques are some of the common physical interventions used by manual therapists to treat neck pain and headaches. There are large well-designed epidemiologic, clinical studies and reviews reporting CSM to be a safe and effective treatment of neck pain and headache. [19–25] A recent population-based, case-control, and case-crossover study found that there was no excess risk of VBA stroke after chiropractic care for neck pain and headaches when compared with physician care.  At the ecologic level, the increase in VBA stroke does not seem to be associated with an increase in the rate of chiropractic use.  However, at the mechanistic level, few studies have examined the effects of CSM on VA blood flow. This has led to uncertainty on whether there is a potential risk in apparently healthy individuals for minor trauma or altered hemodynamics in cervical blood vessels from these maneuvers. Using Doppler ultrasound, Licht and colleagues  observed increased blood flow in the VA of dissected pigs lasting 40 seconds after receiving CSM. When examining the effects of CSM on human VA blood flow, Licht et al. [18, 28] reported no significant difference in VA blood flow between a CSM group and a control group. The limited number of trials, inconsistencies within the results, and poor methodology make conclusions about the effects of CSM on VA blood flow difficult to interpret.
Ultrasonography studies are the most common techniques used to evaluate blood flow in the vertebral arteries. Although ultrasound techniques have been shown to be reliable, produce an image in real time, and are relatively inexpensive, [29–31] they are hampered by its user dependency, limited insonation angles, and unidirectional velocity encoding. [32, 33] When imaging the vertebral arteries, there are additional challenges. Approximately 7% cannot be imaged because of their depth  and ultrasound waves cannot pass through bone, limiting visualization of portions of the VA that pass through osseous foraminae.  Furthermore, surface-based ultrasound lacks resolution when compared with other imaging techniques. [29, 30, 35, 36] This limits visualization to only gross alterations in vessel size,  hindering the ability to locate any anatomical abnormality directly, and demonstrates the results of anatomical disruption as a variation in flow.  Subtle changes such as mild stenosis resulting in hemodynamic flow changes of less than 50% may also be missed by the ultrasound. [29, 30, 38]
Imaging blood flow across a range of cervical spine positions, including rotation and manipulation in vivo, under clinically relevant circumstances has the potential to provide a systematic estimate of alterations to the cerebrovascular hemodynamics. Magnetic resonance imaging (MRI) techniques such as phase-contrast magnetic resonance angiography have greater sensitivity than standard techniques such as Doppler ultrasound and are considered the criterion standard for both diagnosis of VBA strokes [8, 29, 37–39] and blood-flow volume quantification. [35, 40] The intrinsic sensitivity of MRI to flow offers the possibility of analyzing blood flow hemodynamics without restrictions to anatomical coverage or flow direction.  Examining VA flow after various head positions and manipulation using phase-contrast MRI has yet to be reported. Therefore, the purpose of this study was to observe VA blood flow after manipulation and various head positions to assist in the understanding of the extent to which head/neck motion may interact with VA blood flow as a direct contributor to VBA stroke.
This study contributes to a limited body of knowledge regarding the vascular impacts of head position and cervical manipulation and is the first to obtain direct flow and velocity data across a range of mechanical challenges to the cervical spine.
No significant differences were observed in either blood flow or blood velocity of the V3 VA segment after head rotation or from high-velocity, low-amplitude manipulation procedure in healthy young male participants. A trend toward significance in mean flow was noted only when contralateral and ipsilateral VA data were pooled (P = .051). Based on the variation in magnitude of response from different head positions, it is difficult to suggest any trend. Ho et al  state that physiologic variation, vessel anatomical variation, respiratory vessel movement, inconsistent definition of the vessel boundary, and the general condition of participant can result in MRI phase-contrast measurement error. Poor resolution of vessel edge and partial volume effects are other sources of random noise in flow quantification. [40, 48] Standardization of technique, with an imaging modality known to be accurate, reliable, and reproducible, [40, 49] was used to minimize these error sources.
The results regarding the quality of the CSM from the participant and clinician's perspectives have similarities to what is reported in the literature. Rating of force values was within the ranges of force from clinically relevant high-velocity, low-amplitude procedures  performed by trained operators. That the operator in this work reported lower force levels likely reflects the difference in experience between the participants, who themselves are familiar with and in training for these procedures and the operator with more than 30 years' experience. Two studies, Descarreaux et al, [50, 51] and Triano et al [50, 51] examining the maturation of skill in delivery of manipulation procedures, note that more experienced operators provide higher force rates (speed) in trade-off for lower-force amplitudes. [50, 51]
The slight reduction of contralateral mean velocities with cervical rotation observed in this study is consistent with the findings in a recent meta-analysis of Doppler US studies of VA response associated with cervical spine rotation in adults.  Eight of the 9 studies examined found a decrease in contralateral mean blood velocity (in centimeters per second). Furthermore, only 2 trials have examined the effects of CSM on human VA blood flow. [18, 28] Licht et al.  examined peak velocity in the VA after CSM on 20 students with biomechanical cervical spine dysfunction in a randomized controlled trial using Doppler ultrasound. Similar to the MRI data reported here, there was no significant change in peak velocity between the CSM group and a control sample. In another randomized controlled trial color-coded duplex sonography, Licht and colleagues  found no change in VA blood flow with change in head position or after CSM on blood flow.
Considering the trend of a small reduction in flow, the most relevant question is whether such differences are clinically meaningful. Consistent with the hypothesis of potential arterial stenosis secondary to CSM and head rotation, guidance can be found in the literature with respect to diagnosis of stenoses. A diameter reduction of 50% (75% area reduction) is often referred to as “hemodynamically significant” stenosis.  Staub et al  found “nonsignificant” stenosis for the renal artery as being narrowing less than 50% using arteriography color-coded duplex sonography. Peak arterial velocities for more than 50% stenosis were 200 cm/s. The authors report diagnostic sensitivity of 92% and specificity of 81%. Similarly, for the VA, more than 50% stenosis is associated with greater than 108-cm/s peak flow (sensitivity, 96%; specificity, 89%) and an end-diastolic flow of 36 cm/s.  Using these kinds of reference points, Licht et al.  calculated that changes in peak velocity of greater than 25% from baseline are considered clinically relevant. Furthermore, Seidel et al  state that values well below 200 mL/min are within the reference range for net VA flow volume and consider flow volume of less than approximately 100 mL/min an indication of low VA flow.
For the data reported in the present work, arterial flows were never more than half of the end-diastolic flows seen in the reports of confirmed stenosis by Yurdakul and Tola  and are fully within the reference range after all head positions and CSM. The largest changes were observed during contralateral rotation, whereby the VA velocity after CSM was 8% lower than the neutral position and 9% lower than the intermediate position for peak velocity measures. When examining VA flows, the largest change was 7%, which was observed in the contralateral VA after CSM. These relative blood flow changes are small and, according to Licht et al, are not considered clinically relevant. Seidel et al  measured normal flow volumes in healthy participants, finding a wide variation. Although not significantly different, mean (SD) volumes (77.2 [29.8] mL/min) were lower on the right and higher on the left (105.3 [46.4] mL/min). Both the ipsilateral flow at 112.5 mL/min and the contralateral flow at 88.5 mL/min are within the reference ranges published by Seidel et al.
Vertebrobasilar artery stroke can occur for a number of reasons. In the case of trivial traumatic events, the theoretical focus is on mechanical force associated with head movement induces irritation or damage to the intimal lining and resulting in either vasospasm or tearing of the VA, altering blood flow.  The popular conjecture that head rotation, including CSM, may result in stretching, and compression of the VA leading to a decrease in the cross-sectional area of the vessel  was not directly tested in our study. No direct arteriography was performed. Considering the kinematics of the cervical spine during rotation, it seems plausible that there may be mechanical changes to the VA. However, in cadaveric studies, Symons et al  and Wuest et al  measured the axial forces sustained by the VAs during range of motion, injury testing, and various CSMs using paired piezoelectric crystals sewn within the arterial wall. Cervical spinal manipulation produced lower strain values than those associated with physiologic neck rotation. In addition, Austin et al  found that cadaveric rabbit arterial tissue of similar size, structure, and mechanical properties to the human VA does not incur microstructural damage when exposed to 1000 strain cycles of magnitude and speed corresponding to the maximal values observed in the human cadaveric VA during CSM to the neck.
There are several limitations to the study methods. The sample size was small and therefore limits the generalizability conclusions and the number of parameters that can be statistically tested. Random sequencing of head positions, intended to control for any sequencing effects, requires reliance on the existing literature for understanding of neutral, resting flows. The time interval between head condition application and arterial flow quantification was potentially large enough that any transient effect of head movement may have been missed. In addition, postmaneuver analysis makes comparison with other real-time studies difficult and can therefore only describe postprocedural effects rather than effects that occur during a specific maneuver. Although flow quantification demonstrates good test retest comparison, intraobserver variation was not directly analyzed. Magnetic resonance imaging is identified as the most accurate quantification of flow in the literature; however, physiologic variation, vessel anatomical variation, respiratory vessel movement, inconsistent definition of the vessel boundary, and the general condition of participant can result in technical difficulties and variation in flow measures. Cerebral circulation is not limited to the VA contributions but includes flow from the carotid arteries, which were not measured. Finally, peripheral gating for image acquisition combined with the inability to guarantee precisely orthogonal cross sections may underestimate arterial flows.
Evaluation of sample populations deemed of higher risk than healthy adult men may be warranted; however, based on the literature, such criteria are unclear.
Phase-contrast MRI measure of blood velocity and flow through the V3 segment of the VA showed no significant changes in association with either head rotations or chiropractic CSM procedure. No evidence of cerebrovascular hemodynamic effects as a result of mechanical interactions with the VA during head motions was identified.