Abstract
Background: Second harmonic imaging is a new ultrasound technique that allows evaluation of brain tissue perfusion after application of an ultrasound contrast agent.
Objective: To evaluate the potential of this technique for the assessment of abnormal echo contrast characteristics of different brain tumours.
Methods: 27 patients with brain tumours were studied. These were divided into four groups: gliomas, WHO grade III–IV (n = 6); meningiomas (n = 9); metastases (n = 5); and others (n = 7). Patients were examined by second harmonic imaging in a transverse axial insonation plane using the transtemporal approach. Following intravenous administration of 4 g (400 mg/ml) of a galactose based echo contrast agent, 62 time triggered images (one image per 2.5 seconds) were recorded and analysed off-line. Time–intensity curves of two regions of interest (tumour tissue and healthy brain tissue), including peak intensity (PI) (dB), time to peak intensity (TP) (s), and positive gradient (PG) (dB/s), as well as ratios of the peak intensities of the two regions of interest, were derived from the data and compared intraindividually and interindividually.
Results: After administration of the contrast agent a marked enhancement of echo contrast was visible in the tumour tissue in all patients. Mean PI and PG were significantly higher in tumour tissue than in healthy brain parenchyma (11.8 v 5.1 dB and 0.69 v 0.16 dB/s; p < 0.001). TP did not differ significantly (37.1 v 50.2 s; p = 0.14). A tendency towards higher PI and PG as well as shorter TP was apparent in malignant gliomas. When comparing different tumour types, however, none of these variables reached significance, nor were there significant differences between malignant and benign tumours in general.
Conclusions: Second harmonic imaging not only allows identification of brain tumours, but may also help in distinguishing between different tumour types. It gives additional and alternative information about tumour perfusion. Further studies are needed to evaluate the clinical potential of this technique in investigating brain tumours—for example in follow up investigations of patients undergoing radiation or chemotherapy—especially in comparison with neuroradiological and neuropathological findings.
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Selected References
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- Becker G., Hofmann E., Woydt M., Hülsmann U., Mäurer M., Lindner A., Becker T., Krone A. Postoperative neuroimaging of high-grade gliomas: comparison of transcranial sonography, magnetic resonance imaging, and computed tomography. Neurosurgery. 1999 Mar;44(3):469–478. doi: 10.1097/00006123-199903000-00016. [DOI] [PubMed] [Google Scholar]
- Blomley M. J., Cooke J. C., Unger E. C., Monaghan M. J., Cosgrove D. O. Microbubble contrast agents: a new era in ultrasound. BMJ. 2001 May 19;322(7296):1222–1225. doi: 10.1136/bmj.322.7296.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burns P. N. Harmonic imaging with ultrasound contrast agents. Clin Radiol. 1996 Feb;51 (Suppl 1):50–55. [PubMed] [Google Scholar]
- Burns P. N., Wilson S. R., Simpson D. H. Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast. Invest Radiol. 2000 Jan;35(1):58–71. doi: 10.1097/00004424-200001000-00007. [DOI] [PubMed] [Google Scholar]
- Camargo E. E. Brain SPECT in neurology and psychiatry. J Nucl Med. 2001 Apr;42(4):611–623. [PubMed] [Google Scholar]
- Federlein J., Postert T., Meves S., Weber S., Przuntek H., Büttner T. Ultrasonic evaluation of pathological brain perfusion in acute stroke using second harmonic imaging. J Neurol Neurosurg Psychiatry. 2000 Nov;69(5):616–622. doi: 10.1136/jnnp.69.5.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster F. S., Burns P. N., Simpson D. H., Wilson S. R., Christopher D. A., Goertz D. E. Ultrasound for the visualization and quantification of tumor microcirculation. Cancer Metastasis Rev. 2000;19(1-2):131–138. doi: 10.1023/a:1026541510549. [DOI] [PubMed] [Google Scholar]
- Frinking P. J., Bouakaz A., Kirkhorn J., Ten Cate F. J., de Jong N. Ultrasound contrast imaging: current and new potential methods. Ultrasound Med Biol. 2000 Jul;26(6):965–975. doi: 10.1016/s0301-5629(00)00229-5. [DOI] [PubMed] [Google Scholar]
- Gillard J. H., Minhas P. S., Hayball M. P., Bearcroft P. W., Antoun N. M., Freer C. E., Mathews J. C., Miles K. A., Pickard J. D. Assessment of quantitative computed tomographic cerebral perfusion imaging with H2(15)O positron emission tomography. Neurol Res. 2000 Jul;22(5):457–464. doi: 10.1080/01616412.2000.11740700. [DOI] [PubMed] [Google Scholar]
- Hancock J., Dittrich H., Jewitt D. E., Monaghan M. J. Evaluation of myocardial, hepatic, and renal perfusion in a variety of clinical conditions using an intravenous ultrasound contrast agent (Optison) and second harmonic imaging. Heart. 1999 Jun;81(6):636–641. doi: 10.1136/hrt.81.6.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrer Judith U., Klötzsch Christof. Second harmonic imaging of the human brain: the practicability of coronal insonation planes and alternative perfusion parameters. Stroke. 2002 Jun;33(6):1530–1535. doi: 10.1161/01.str.0000016402.42083.9d. [DOI] [PubMed] [Google Scholar]
- Heckemann R. A., Cosgrove D. O., Blomley M. J., Eckersley R. J., Harvey C. J., Mine Y. Liver lesions: intermittent second-harmonic gray-scale US can increase conspicuity with microbubble contrast material-early experience. Radiology. 2000 Aug;216(2):592–596. doi: 10.1148/radiology.216.2.r00au31592. [DOI] [PubMed] [Google Scholar]
- Kim T. K., Choi B. I., Han J. K., Hong H. S., Park S. H., Moon S. G. Hepatic tumors: contrast agent-enhancement patterns with pulse-inversion harmonic US. Radiology. 2000 Aug;216(2):411–417. doi: 10.1148/radiology.216.2.r00jl21411. [DOI] [PubMed] [Google Scholar]
- Kuhn E. Myotonia congenita (Thomsen) und rezessive generalisierte Myotonie (Becker). Nervenarzt. 1993 Dec;64(12):766–769. [PubMed] [Google Scholar]
- Lev MH, Hochberg F. Perfusion Magnetic Resonance Imaging to Assess Brain Tumor Responses to New Therapies. Cancer Control. 1998 Mar;5(2):115–123. doi: 10.1177/107327489800500202. [DOI] [PubMed] [Google Scholar]
- Meyer K., Seidel G., Knopp U. Transcranial sonography of brain tumors in the adult: an in vitro and in vivo study. J Neuroimaging. 2001 Jul;11(3):287–292. doi: 10.1111/j.1552-6569.2001.tb00048.x. [DOI] [PubMed] [Google Scholar]
- Mirzai S., Samii M. Current status and future challenges in cerebral blood flow mapping in intracranial tumors. Keio J Med. 2000 Feb;49 (Suppl 1):A16–A24. [PubMed] [Google Scholar]
- Nelson S. J. Analysis of volume MRI and MR spectroscopic imaging data for the evaluation of patients with brain tumors. Magn Reson Med. 2001 Aug;46(2):228–239. doi: 10.1002/mrm.1183. [DOI] [PubMed] [Google Scholar]
- Porter T. R., Li S., Kricsfeld D., Armbruster R. W. Detection of myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles using transient response second harmonic imaging. J Am Coll Cardiol. 1997 Mar 15;29(4):791–799. doi: 10.1016/s0735-1097(96)00575-x. [DOI] [PubMed] [Google Scholar]
- Postert T., Federlein J., Rose J., Przuntek H., Weber S., Büttner T. Ultrasonic assessment of physiological echo-contrast agent distribution in brain parenchyma with transient response second harmonic imaging. J Neuroimaging. 2001 Jan;11(1):18–24. doi: 10.1111/j.1552-6569.2001.tb00004.x. [DOI] [PubMed] [Google Scholar]
- Postert T., Muhs A., Meves S., Federlein J., Przuntek H., Büttner T. Transient response harmonic imaging: an ultrasound technique related to brain perfusion. Stroke. 1998 Sep;29(9):1901–1907. doi: 10.1161/01.str.29.9.1901. [DOI] [PubMed] [Google Scholar]
- Sboros V., Moran C. M., Anderson T., McDicken W. N. An in vitro comparison of ultrasonic contrast agents in solutions with varying air levels. Ultrasound Med Biol. 2000 Jun;26(5):807–818. doi: 10.1016/s0301-5629(00)00215-5. [DOI] [PubMed] [Google Scholar]
- Schrope B. A., Newhouse V. L. Second harmonic ultrasonic blood perfusion measurement. Ultrasound Med Biol. 1993;19(7):567–579. doi: 10.1016/0301-5629(93)90080-8. [DOI] [PubMed] [Google Scholar]
- Seidel G., Meyer K. Harmonic imaging--a new method for the sonographic assessment of cerebral perfusion. Eur J Ultrasound. 2001 Dec;14(2-3):103–113. doi: 10.1016/s0929-8266(01)00151-3. [DOI] [PubMed] [Google Scholar]
- Seidel G., Vidal-Langwasser M., Algermissen C., Gerriets T., Kaps M. The influence of Doppler system settings on the clearance kinetics of different ultrasound contrast agents. Eur J Ultrasound. 1999 May;9(2):167–175. doi: 10.1016/s0929-8266(99)00026-9. [DOI] [PubMed] [Google Scholar]
- Sugahara T., Korogi Y., Kochi M., Ushio Y., Takahashi M. Perfusion-sensitive MR imaging of gliomas: comparison between gradient-echo and spin-echo echo-planar imaging techniques. AJNR Am J Neuroradiol. 2001 Aug;22(7):1306–1315. [PMC free article] [PubMed] [Google Scholar]
- Vordermark D., Becker G., Flentje M., Richter S., Goerttler-Krauspe I., Koelbl O. Transcranial sonography: integration into target volume definition for glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2000 Jun 1;47(3):565–571. doi: 10.1016/s0360-3016(00)00565-4. [DOI] [PubMed] [Google Scholar]
- Wilson S. R., Burns P. N. Liver mass evaluation with ultrasound: the impact of microbubble contrast agents and pulse inversion imaging. Semin Liver Dis. 2001 May;21(2):147–159. doi: 10.1055/s-2001-15342. [DOI] [PubMed] [Google Scholar]
- Wilson S. R., Burns P. N., Muradali D., Wilson J. A., Lai X. Harmonic hepatic US with microbubble contrast agent: initial experience showing improved characterization of hemangioma, hepatocellular carcinoma, and metastasis. Radiology. 2000 Apr;215(1):153–161. doi: 10.1148/radiology.215.1.r00ap08153. [DOI] [PubMed] [Google Scholar]
- Zhang J., George A. L., Jr, Griggs R. C., Fouad G. T., Roberts J., Kwieciński H., Connolly A. M., Ptácek L. J. Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita. Neurology. 1996 Oct;47(4):993–998. doi: 10.1212/wnl.47.4.993. [DOI] [PubMed] [Google Scholar]
- de Jong N., Ten Cate F. J., Lancée C. T., Roelandt J. R., Bom N. Principles and recent developments in ultrasound contrast agents. Ultrasonics. 1991 Jul;29(4):324–330. doi: 10.1016/0041-624x(91)90030-c. [DOI] [PubMed] [Google Scholar]