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Refined analysis of transcranial Doppler HITS
Reflection & Reaction Refined analysis of transcranial Doppler HITS Transcranial Doppler is used in several specialised centres to detect microembolic signals in the cerebral circulation. This technique, which was first reported almost two decades ago,1 may benefit patients who are at increased risk during interventional investigations and carotid surgery.2 To detect microembolic signals a Doppler probe with a frequency of approximately 2 MHz is fixed over the temporal bone—its position, orientation, and the Doppler sample volume depth are adjusted to obtain a good signal from the ipsilateral middle cerebral artery. Since a microembolus has different acoustic properties to the blood in which it is travelling, there is a transient increase in the echo intensity as it passes through the Doppler sample volume. This is known as a high intensity transient signal (HITS). Careful monitoring of the Doppler signal can therefore provide a means of classification and artifact rejection. To date, most studies have relied on trained observers to identify potential emboli, and to distinguish between true embolic signals and those caused by other mechanisms. There are, however, several drawbacks to this approach in terms of both cost and reliability. If the technique is to become widely accepted in clinical practice, then some form of automatic recognition is essential. Attempts have been made to provide commercial automated systems but none have been independently shown to discriminate artifacts from microemboli. Such systems must also be able to distinguish between signals from emboli of different types because the clinical consequences of microemboli, although presently unclear, are thought to vary greatly. Accordingly, studies have tried to differentiate between the signals from different types of emboli, but all have at least one drawback, and researchers are still seeking a truly reliable method of characterising the composition of individual emboli. Brucher and Russell3,4 recently showed that a multifrequency Doppler instrument was better for automatic microembolic signal detection and artifact rejection than anything else tested so far. Embolus versus artifact
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recognition was achieved by use of four procedures: comparison of the Doppler shifts recorded from simultaneously applied 2·0 MHz and 2·5 MHz frequencies; measurement of the maximum duration taken for an embolus to travel through the sample volume; recording of signals from successive gates placed along the course of the vessel; and demonstration of the passage of solid material with a time delay of >4 ms. Studies in vitro with plastic microspheres (>80 m in diameter) representative of solid particles, gas bubbles (8–25 m in diameter) such as those commonly seen in patients with mechanical heart valves, and artifacts introduced by various tapping in a closed loop system showed a 99% correct classification. Tests in patients with mechanical heart valves and carotid stenosis confirmed that microembolus versus artifact classification was better than 98%. Furthermore, solid and gaseous material could be differentiated with 95% accuracy. Of particular interest is the introduction of the “quarter Doppler shift” as a new way to describe different Doppler shift frequencies that are recorded for an embolus or gas particle when insonating simultaneously with two frequencies (1·25 kHz and 1·0 kHz). For practical purposes, this parameter assumes a linear relation of the embolus-to-blood ratio for particulate material with diameters below 300 m (as opposed to gaseous emboli) with little change in the Doppler shift frequencies used by the system. Indeed, this appears to offer good discrimination for this size of solid emboli. However, the backscatter crosssection for particulate emboli larger than 300 m is more complex. For larger, perhaps more clinically relevant particulate emboli, substantial differences in Doppler frequency shifts are likely to be observed for the two recording frequencies. This may limit the automatic discrimination of larger emboli and gases, even if overloading is prevented. Further studies will be required to find out whether these theoretical considerations will change the automated detection of HITS in the clinical setting.
If the use of embolus detection is to reach its full potential, both in clinical trials and in routine monitoring, automatic methods of processing Doppler data, so that large amounts of information can be speedily and accurately evaluated, will be necessary. As novel applications for dynamic quantitative measurement of cerebral perfusion with second generation ultrasound contrast agents emerge,5,6 new approaches with systems that can automatically analyse multiple gaseous particles may prove advantageous. Such techniques could be employed, for example, to identify embolus material by use of targeted microbubbles that attach to solid emboli so that their characteristics can be established from their bubble signatures. This approach is being investigated in the recently launched EC-funded project for “Ultrasonographic monitoring and early diagnosis of stroke”. Moreover, exciting new applications for sitespecific monitoring of microbubbles in ultrasound-mediated gene therapy are also conceivable. Indeed, such extended applications of this monitoring technique, originally designed for embolus detection, may significantly increase its clinical relevance and serve to promote further advances in this important field of ultrasound. MG Hennerici and S Meairs Department of Neurology, Ruprecht-KarlsUniversität Heidelberg, Universitätsklinikum Mannheim, D-68135 Mannheim, Germany. Email [email protected] References 1
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Padayachee TS, Gosling RG, Bishop CC, Burnand K, Browse NL. Monitoring middle cerebral artery blood velocity during carotid endarterectomy. Br J Surg 1986; 73: 98–100. Naylor AR. Transcranial Doppler monitoring during carotid endarterectomy. In: Hennerici M, Meairs S, eds. Cerebrovascular Ultrasound—theory, practice and future developments. Cambridge: Cambridge University Press, 2001: 317–23. Russell D, Brucher R. Online automatic discrimination between solid and gaseous cerebral microemboli with the first multifrequency transcranial Doppler. Stroke 2002; 33: 1975–80. Brucher R, Russell D. Automatic online embolus detection and artifact rejection with the first multifrequency transcranial Doppler. Stroke 2002; 33: 1969–74. Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 1998; 97: 473–83. Meairs S, Daffertshofer M, Neff W, Eschenfelder C, Hennerici M. Pulse-inversion contrast harmonic imaging: ultrasonographic assessment of cerebral perfusion. Lancet 2000; 355: 550–51.
THE LANCET Neurology Vol 1 November 2002
http://neurology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
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recognition was achieved by use of four procedures: comparison of the Doppler shifts recorded from simultaneously applied 2·0 MHz and 2·5 MHz frequencies; measurement of the maximum duration taken for an embolus to travel through the sample volume; recording of signals from successive gates placed along the course of the vessel; and demonstration of the passage of solid material with a time delay of >4 ms. Studies in vitro with plastic microspheres (>80 m in diameter) representative of solid particles, gas bubbles (8–25 m in diameter) such as those commonly seen in patients with mechanical heart valves, and artifacts introduced by various tapping in a closed loop system showed a 99% correct classification. Tests in patients with mechanical heart valves and carotid stenosis confirmed that microembolus versus artifact classification was better than 98%. Furthermore, solid and gaseous material could be differentiated with 95% accuracy. Of particular interest is the introduction of the “quarter Doppler shift” as a new way to describe different Doppler shift frequencies that are recorded for an embolus or gas particle when insonating simultaneously with two frequencies (1·25 kHz and 1·0 kHz). For practical purposes, this parameter assumes a linear relation of the embolus-to-blood ratio for particulate material with diameters below 300 m (as opposed to gaseous emboli) with little change in the Doppler shift frequencies used by the system. Indeed, this appears to offer good discrimination for this size of solid emboli. However, the backscatter crosssection for particulate emboli larger than 300 m is more complex. For larger, perhaps more clinically relevant particulate emboli, substantial differences in Doppler frequency shifts are likely to be observed for the two recording frequencies. This may limit the automatic discrimination of larger emboli and gases, even if overloading is prevented. Further studies will be required to find out whether these theoretical considerations will change the automated detection of HITS in the clinical setting.
If the use of embolus detection is to reach its full potential, both in clinical trials and in routine monitoring, automatic methods of processing Doppler data, so that large amounts of information can be speedily and accurately evaluated, will be necessary. As novel applications for dynamic quantitative measurement of cerebral perfusion with second generation ultrasound contrast agents emerge,5,6 new approaches with systems that can automatically analyse multiple gaseous particles may prove advantageous. Such techniques could be employed, for example, to identify embolus material by use of targeted microbubbles that attach to solid emboli so that their characteristics can be established from their bubble signatures. This approach is being investigated in the recently launched EC-funded project for “Ultrasonographic monitoring and early diagnosis of stroke”. Moreover, exciting new applications for sitespecific monitoring of microbubbles in ultrasound-mediated gene therapy are also conceivable. Indeed, such extended applications of this monitoring technique, originally designed for embolus detection, may significantly increase its clinical relevance and serve to promote further advances in this important field of ultrasound. MG Hennerici and S Meairs Department of Neurology, Ruprecht-KarlsUniversität Heidelberg, Universitätsklinikum Mannheim, D-68135 Mannheim, Germany. Email [email protected] References 1
2
3
4
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Padayachee TS, Gosling RG, Bishop CC, Burnand K, Browse NL. Monitoring middle cerebral artery blood velocity during carotid endarterectomy. Br J Surg 1986; 73: 98–100. Naylor AR. Transcranial Doppler monitoring during carotid endarterectomy. In: Hennerici M, Meairs S, eds. Cerebrovascular Ultrasound—theory, practice and future developments. Cambridge: Cambridge University Press, 2001: 317–23. Russell D, Brucher R. Online automatic discrimination between solid and gaseous cerebral microemboli with the first multifrequency transcranial Doppler. Stroke 2002; 33: 1975–80. Brucher R, Russell D. Automatic online embolus detection and artifact rejection with the first multifrequency transcranial Doppler. Stroke 2002; 33: 1969–74. Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 1998; 97: 473–83. Meairs S, Daffertshofer M, Neff W, Eschenfelder C, Hennerici M. Pulse-inversion contrast harmonic imaging: ultrasonographic assessment of cerebral perfusion. Lancet 2000; 355: 550–51.
THE LANCET Neurology Vol 1 November 2002
http://neurology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.