Published online before print October 14, 2004, doi: 10.1161/01.STR.0000144656.77330.18
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(Stroke. 2004;35:2430.)
© 2004 American Heart Association, Inc.
Letters to the Editor |
Near-Infrared Spectroscopy in Stroke: From Research to Clinical Practice
Division of Geriatric Medicine, St George’s Hospital Medical School, University of London, UK
To the Editor:
We read with interest the editorial comment by Villringer and colleagues on the use of near-infrared spectroscopy (NIRS) as a routine diagnostic tool in stroke.1 We agree that NIRS has great potential to become a valuable bedside tool; however, several limitations need to be overcome.
Crucial to the successful use of NIRS is an appreciation of its ability to measure real-time changes in cerebral hemoglobin oxygen saturation. These equate to changes in cerebral blood volume only and not necessarily cerebral blood flow and may consequently lead to misinterpretation of clinical data. The relative contribution of different vascular compartments to the NIRS signal also needs to be established as it is not known whether venous changes in oxygenated hemoglobin makes a greater contribution than arterial changes. Extracranial tissues: melanin-containing skin, lipid-prevalent soft tissue, bone, and cerebrospinal fluid may also absorb a significant proportion of infrared light. This makes absolute intrapatient comparisons difficult. Even in individual patient analyses extracranial tissues may elicit varying degrees of absorption with changes in their extracranial blood supply. Attempts to quantify this contribution have proved difficult whether studying patients at carotid endarterectomy2 or using Monte Carlo simulation.3 Smielewski and colleagues however suggest that cerebral oxygenation, as recorded by NIRS and cutaneous laser-Doppler flowmetry, is largely unaffected by extracranial tissue perfusion.4 More work is needed to understand the behavior of near-infrared light in different biological tissues if NIRS is to be used as a reliable clinical monitor.
NIRS use as a research tool in measuring cortical activation may help in the understanding of dynamic remodeling which may occur within brain architecture during neuroplasticity poststroke. The work of Kato and colleagues using NIRS in conjunction with functional MRI has lent support to the role of activation of the ipsilateral primary sensorimotor and supplementary motor cortex during neuronal reorganization after ischemic stroke.5
The use of NIRS in the acute clinical assessment of cerebral perfusion in stroke has also been supported in recent work by Treborg and colleagues wherein indocyanine green was used as a tracer.6 NIRS has the potential to be used in the noninvasive assessment of the effects of thrombolysis on reperfusion and control of physiological parameters such as blood pressure and oxygenation after stroke. A future role of NIRS in rehabilitation would be to quantify cerebral oxygenation and cerebral blood volume in stroke patients undergoing changes in body position. This would potentially help identify patients who were more vulnerable to cerebral ischemic symptoms while undergoing orthostatic stress.7 In terms of understanding cortical activation during rehabilitation, Saitou and colleagues showed that some tasks such as ergometer use, calculation, and facilitation increased both cerebral blood volume and oxygenation in the affected prefrontal cortex of patients with hemiplegia.8 The use of multichannel NIRS in rehabilitation could help identify topographical areas of the brain activated during functional activity in real-world environments outside the neuroimaging "tunnel."
In summary, there is great potential both acutely and in the rehabilitation setting for NIRS. Qualifying some of the uncertainties around its use will be a necessary precursor to its acceptance, reliability, and use in routine stroke care.
References
1. Villringer A, Steinbrink J, Obrig H. Editorial comment-cerebral near-infrared spectroscopy: how far away from a routine diagnostic tool? Stroke. 2004; 35: 70–72.
2. Kirkpatrick PJ, Lam J, Al-Rawi P, Smielewski P, Czosnyka M. Defining thresholds for critical ischemia by using near-infrared spectroscopy in the adult brain. J Neurosurg. 1998; 89: 389–394.[Medline] [Order article via Infotrieve]
3. Okada E, Delpy DT. Near-infrared light propagation in an adult head model. II. Effect of superficial tissue thickness on the sensitivity of the near-infrared spectroscopy signal Appl Opt. 2003; 42: 2915–2922.
4. Smielewski P, Kirkpatrick P, Minhas P, Pickard JD, Czosnyka M. Can cerebrovascular reactivity be measured with near-infrared spectroscopy? Stroke. 1995; 26: 2285–2292.
5. Kato H, Izumiyama M, Koizumi H, Takahashi A, Itoyama Y. Near-infrared spectroscopic topography as a tool to monitor motor reorganization after hemiparetic stroke: a comparison with functional MRI. Stroke. 2002; 33: 2032–2036.
6. Terborg C, Bramer S, Harscher S, Simon M, Witte OW. Bedside assessment of cerebral perfusion reductions in patients with acute ischaemic stroke by near-infrared spectroscopy and indocyanine green. J Neurol Neurosurg Psychiatry. 2004; 75: 38–42.
7. Mehagnoul-Schipper DJ, Vloet LC, Colier WN, Hoefnagels WH, Jansen RW. Cerebral oxygenation declines in elderly subjects in response to assuming the upright position. Stroke. 2000; 31: 1615–1620.
8. Saitou H, Yanagi H, Hara S, Tsuchiya S, Tomura S. Cerebral blood volume and oxygenation among post stroke hemiplegic patients: effects of 13 rehabilitation tasks measured by near-infrared spectroscopy. Arch Phys Med Rehabil. 2000; 81: 1348–1356.[CrossRef][Medline] [Order article via Infotrieve]
Berlin Neuroimaging Center, Department of Neurology, Charité, Humboldt University, Berlin, Germany
Response:
We fully agree that a critical evaluation of optical topography is required when applied in a clinical context as you point out in the comment regarding our editorial comment.1 Certainly the methodology can as yet not be used in a way similar to neurosonological approaches (transcranial and extracranial Doppler sonography) but it may well gain a similar status with a focus on neuromonitoring in intensive care settings. We are convinced that beyond it being generally wise to follow a skeptical approach when introducing a novel methodology into clinical research, a number of basic tasks are worth the joint effort to establish noninvasive cerebral optical spectroscopy beyond a purely scientific context (for review see2). The following applications seem attainable in near future:
Perfusion Imaging
There is a number of first attempts to use dye-bolus technique to assess a measure of cerebral perfusion.3 Though exact mean transit time (MTT) assessment may be the gold standard,4 it should not be forgotten that a quasi-continuous assessment on a stroke unit may be an exquisite option to monitor the patient. Interhemispheric perfusion differences, even if only semiquantitative, may still help us understand pathophysiologically relevant and potentially treatable changes in perfusion caused by recanalization after embolic occlusion of the larger vessels in acute stroke. This has been done using TCD5 but will greatly profit even from a qualitative assessment of cortical perfusion. There is no need to replace the standard methods; on the contrary, insonation of the large vessels and spectroscopic investigation of cortical perfusion will be complementary. Ideally it will be combined with the high spatial resolution of perfusion weighted MR imaging performed at larger intervals.
Functional Stimulation
There is no reason why the large number of functional stimulation studies performed with near infrared spectroscopy should not be directly transferred to a bed-side assessment in patients suffering from neurovascular or neurodegenerative diseases. The major problem here rather is the reluctance of clinical practice to focus on functional rather than structural brain imaging. The traditional exception is electroencephalography (EEG) and the assessment of visually, somatosensory, and acoustically evoked potentials (VEP/SSEP/AEP), which have been used for decades. The slow introduction into clinical practice is by no means specific to optical methods; Functional magnetic resonance imaging (fMRI) and positron emission tomography share a similar problem. Because spatial resolution of optical topography will most probably not reach that of fMRI techniques, primary cortical areas (motor and visual) may serve as indicators of a normal or disturbed neurovascular coupling. Much like evoked potentials, this will help link evidence of structural lesions (as seen in routine imaging approaches) to the clinical examination (which by no means is objective but still the gold standard when therapeutic success is evaluated).
Neurovascular Coupling
It has been suggested that a number of neurological diseases interfere with the physiologically tight coupling between neuronal and vascular response.6,7 This can be assessed with low-cost, undemanding set-up and at the bed-side when EEG-techniques and optical topography are combined.8 Again, the major obstacle is the fact that clinical studies require a longer and potentially very tedious approach, and as yet few representative studies have been published. This again is a limitation, which necessitates adequate funding rather than shedding doubt of the versatility of optical methods as such.
Our impression is that the state of the art methodological approaches of noninvasive optical imaging techniques presently do allow for studies relevant to clinical practice. The major shortcoming is the reluctance to challenge the method in larger studies, with representative numbers of patients included. At the same time, the research into physiological mechanisms of functional activation has been established. In cooperation with physicists and a practice-oriented engineering effort, cortical functional activation is bound to reach much higher topographical and depth resolution in the very near future.
References
1. Villringer A, Steinbrink J, Obrig H. Editorial comment-cerebral near-infrared spectroscopy: how far away from a routine diagnostic tool? Stroke. 2004; 35: 70–72.
2. Obrig H, Villringer A. Beyond the visible-imaging the human brain with light. J Cereb Blood Flow Metab. 2003; 23: 1–18.[CrossRef][Medline] [Order article via Infotrieve]
3. Terborg C, Bramer S, Harscher S, Simon M, Witte OW. Bedside assessment of cerebral perfusion reductions in patients with acute ischaemic stroke by near-infrared spectroscopy and indocyanine green. J Neurol Neurosurg Psychiatry. 2004; 75: 38–42.
4. Doege CA, Kerskens CM, Romero BI, Brunecker P, Junge-Hulsing J, von Pannwitz W, Muller B, Villringer A. Assessment of diffusion and perfusion deficits in patients with small subcortical ischemia. AJNR Am J Neuroradiol. 2003; 24: 1355–1363.
5. Alexandrov AV, Burgin WS, Demchuk AM, El Mitwalli A, Grotta JC. Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement. Circulation. 2001; 103: 2897–2902.
6. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004; 5: 347–360.[CrossRef][Medline] [Order article via Infotrieve]
7. Villringer A, Dirnagl U. Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging. Cerebrovasc Brain Metab Rev. 1995; 7: 240–276.[Medline] [Order article via Infotrieve]
8. Obrig H, Israel H, Kohl-Bareis M, Uludag K, Wenzel R, Muller B, Arnold G, Villringer A. Habituation of the visually evoked potential and its vascular response: implications for neurovascular coupling in the healthy adult. Neuroimage. 2002; 17: 1–18.[CrossRef][Medline] [Order article via Infotrieve]
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