From the Department of Neurology, Ruhr-University Bochum (Germany).
Correspondence to Dr Thomas Postert, Department of Neurology, St Josef Hospital, Ruhr-University Bochum, Gudrunstraße 56, 44791 Bochum, Germany.
Methods—In 18 patients without cerebrovascular diseases, TRsHI
examinations were performed bilaterally with the use of the
transtemporal approach after application of 6.5 mL of a
galactose-based microbubble suspension (400 mg/mL). The transmission
rate was once every 4 cardiac cycles. Regional cerebral contrast was
visually assessed and then quantified off-line with the use of
time-intensity curves. In 4 different regions of interest (ROI)
(posterior part of the thalamus [ROIa], anterior part of the thalamus
[ROIb], lentiform nucleus [ROIc], and white matter [ROId]), the
following parameters were evaluated: peak intensity, area
under the curve (AUC), and time to peak intensity. AUC ratios for
ROIc/a, d/a, c/b, and d/b were calculated.
Results—In all patients parenchymal contrast enhancement was
visually detectable. One hundred thirty-one characteristic
time-intensity curves (baseline phase, peak contrast intensity, slow
washout phase) were demonstrable in 144 ROIs. In ROIc and ROId,
characteristic contrast curves could be observed most frequently (68/72
examinations), whereas time-intensity curves in ROIa and ROIb could not
be evaluated because of inadequate contrast enhancement in 9 of 72
examinations. Time to peak intensity varied between 20 and 52 cardiac
cycles; in 1 patient it was 88 cardiac cycles. In all individuals AUCs
and in 16 of 18 subjects peak intensity in ROIc and ROId showed
a 2- to 10-fold increase compared with ROIa and ROIb. In no examination
did AUC ratios show a >2-fold side difference irrespective of the
ROI.
Conclusions—The present study demonstrates for the first time
that TRsHI produces accurate contrast in different brain areas and
represents an ultrasonic tool related to brain perfusion.
Absolute values of quantitative parameters show high
variations caused by different temporal bone thicknesses and a complex
relationship between echo contrast concentrations and measurements of
optic intensities. Ratios between different ROIs help to compare
contrast enhancement in different brain areas. Furthermore, because of
the fact that attenuation of contrast enhancement in TRsHI depends
strictly on the insonation depth, harmonic imaging studies of brain
perfusion cannot be compared directly with other imaging techniques
such as positron emission tomography.
Transcranial Sonography
Anatomic localization of different ROIs is illustrated in Figure 1
For intraindividual comparison between right and left examination
sides, ratios of the parameters in different ROIs were
calculated for evaluation and comparison of side-dependent contrast
enhancement. The following parameters were divided:
AUCc/AUCa, AUCd/AUCa, AUCc/AUCb, and AUCd/AUCb. AUC values in different
ROIs and ratios between examination sides were compared with the
Wilcoxon signed rank test (paired nonparametric
test).
Quantitative Analysis of Time-Intensity Curves
Comparison Between Both Examination Sides
AUC Ratios of ROIs
Preliminary echocardiographic studies demonstrated the
potential of HI for the noninvasive detection of myocardial perfusion
in humans in a variety of clinical settings.6 18
Additional use of TR imaging has been shown to prevent the destruction
of microbubbles and is regarded as a helpful supplementary tool for
HI6 .
In the present study we succeeded for
the first time in visualizing parenchymal cerebral contrast with
ultrasound. Visually evident contrast could be assessed quantitatively
in different brain areas. In areas with marked contrast enhancement
caused by the ultrasound contrast agent, a mean gain of 15.3 dB (range,
3 to 54 dB) was observed. This mean signal increase is comparable to
that in liver (20.5 dB)7 and myocardial (17 to 37
dB)5 examinations. High peak values in our study
(54 dB) are mainly attributed to the high echo contrast concentrations
compared with liver and myocardial investigations. For physical reasons
TRsHI results of brain parenchyma show a different pattern of contrast
distribution compared with other imaging techniques. First, it is
important to note that ultrasound attenuation is dependent on frequency
and image depth. Therefore, backscattered ultrasound signals at the
second harmonic frequency will be attenuated approximately twice as
much as signals of the fundamental frequency. Furthermore, the deeper
figured the structure is, the greater the attenuation will be. This
effect will occur twice as fast at the second harmonic than at the
fundamental frequency.19 20 Second, the
relationship between concentrations of microbubbles and measurements of
optic intensity is complicated because of the acoustic properties of
echo contrast agents and signal processing of ultrasound scanners. This
refers not only to TRsHI studies but to quantitative measurements of
echo contrast concentrations in general. At low microbubble
concentrations, a linear relationship between microbubble concentration
and optic intensity can be observed. For higher concentrations
(>30 000 bubbles per cubic centimeter), backscatter intensity
saturates, and an additional increase in tracer concentration cannot be
registered as an increase in optic
intensity.10 21 This fact explains why
AUCs and PI may appear equal despite different flow rates and why AUC
and PI of time-intensity curves cannot be related directly to cerebral
perfusion unless these parameters are not calibrated.
Echocardiographic studies have shown that the
correlation between blood flow and echo contrast agent improved when a
polynomial function was applied to the data.22
For this reason a standardization of the relationship between tracer
concentration and system response is needed to derive quantitative data
directly from time-intensity curves. Depth-dependent attenuation of
TRsHI examinations and nonlinear signal processing explain that this
ultrasound technique cannot be compared with other imaging techniques
assessing brain perfusion, such as positron emission tomography
(PET).
However, our results show that contrast enhancement may be placed in
some relation to cerebral perfusion if the physical properties of TRsHI
are taken into account. Corresponding to the functional activity,
regional blood flow values show distinct differences in PET studies.
Perfusion of the white matter (20 mL/100 g per minute) is found to be
lower than that of the basal ganglia (60 to 70 mL/100 g per
minute).23 24 In our study gray-scale contrast
intensities after echo contrast application were comparable for the
white matter and the lentiform nucleus; the thalamus exhibited a lower
signal intensity. Because of the different insonation depths of these
areas, ultrasound reflection of the lentiform nucleus is more
attenuated than the white matter, thus simulating a similar perfusion
in these regions. Furthermore, thalamic contrast enhancement exhibits
the highest attenuation of the ultrasound waves in comparison to the
other ROIs. In additional studies including more patients,
depth-adjusted amplification factors for each region may be developed
that may allow direct comparison of blood perfusion with PET studies
irrespective of insonation depth. The side difference of AUC ratios did
not exceed factor 2 in any patient. The comparison of left- and
right-sided AUC ratios can partially compensate for the great
interindividual differences of TRsHI values.
Apart from nonlinear signal processing, high interindividual variations
of absolute values and side differences in the quantitative
analysis of TRsHI examinations in our study may be explained by
temporal bone thickness and the attenuation of the backscattered second
harmonic frequency. Small variations of bone thickness in the same
individual may potentiate asymmetric attenuation of the second harmonic
frequency (3.6 MHz); marked differences of bone thickness in different
subjects may cause misleading absolute values.
A further limitation of TRsHI is due to the limited spatial resolution
of transcranial real-time sonography. Since the lentiform
nucleus and the white matter appear isoechogenic to surrounding brain
parenchyma9 in transcranial real-time
images, precise anatomic localization of contrast enhancement in these
areas is difficult. It cannot be excluded that parts of the internal
capsule and the lentiform nucleus are included in ROIb; in ROIa parts
of the internal capsule may be incorporated. For this reason
experienced ultrasound examiners are necessary to accurately visualize
the third ventricle and the thalamus as landmarks for orientation.
Although extended time intervals between frame rates produce prolonged
contrast, it may be impractical in some patients to hold the transducer
in 1 position for a period of
In conclusion, the present study demonstrates that qualitative and
to a minor extent quantitative TRsHI is applicable to neurosonology and
provides characteristic phases of contrast enhancement and fading
contrast effect in different brain areas. Our study indicates that
gray-scale TRsHI provides detection of ultrasound contrast in brain
parenchyma by improving the signal to noise ratio. It is a promising
and noninvasive new method for visualization of focal cerebral contrast
enhancement, allowing real-time "digital subtraction" imaging of
capillary blood flow in the brain with ultrasound. Because TRsHI can be
rapidly performed as a bedside examination, this technique may be a
cost-effective method of detecting abnormalities of echo contrast
enhancement, particularly in cerebrovascular diseases.
Received March 31, 1998;
revision received May 26, 1998;
accepted June 18, 1998.
2.
Schrope BA, Newhouse VL, Uhlendorf V. Simulated
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Tucker DG, Welsby VG. Ultrasonic monitoring of
decompression. Lancet.. 1968;1:1253. Abstract.
5.
Porter TR, Xie F, Kricsfeld D, Armbruster RW. Improved
myocardial contrast with second harmonic transient ultrasound response
imaging in humans using intravenous perfluorocarbon-exposed
sonicated dextrose albumin. J Am Coll Cardiol. 1996;27:1497–1501.[Abstract]
6.
Porter TR, Li S, Kricsfeld D, Armbruster RW. Detection
of myocardial perfusion in multiple echocardiographic
windows with one intravenous injection of microbubbles
using transient response second harmonic imaging. J Am Coll
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7.
Yuko K, Moriyasu F, Mine Y, Nada T, Kamiyama N,
Suginoshita Y, Matsumura T, Kobayashi K, Chiba T. Gray-scale second
harmonic imaging of the liver with galactose-based microbubbles.
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R. Acoustic bubble destruction is a possible mechanism for transient
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Abstract.
9.
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Meurers B. Transcranial color-coded real-time sonography in
adults. Stroke. 1990;21:1680–1688.
10.
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in quantitative contrast echocardiography: the
steps to quantitation of perfusion. J Am Soc
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11.
Kaps M, Schaffer P, Beller KD, Seidel G, Bliesath H,
Wurst W. Phase I: transcranial echo contrast studies in
healthy volunteers. Stroke. 1995;26:2048–2052.
12.
Postert T, Büttner T, Federlein J, Przuntek H.
Insufficient and absent acoustic temporal bone window: potential and
limitations of transcranial contrast-enhanced color-coded
sonography and contrast-enhanced power-based sonography.
Ultrasound Med Biol. 1997;23:857–862.[Medline]
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sonography. Stroke. 1993;24:676–684.
14.
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Herrmann C, Rivoir A, Müri RM. Contrast-enhanced
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cerebrovascular disease. Stroke. 1997;28:2473–2478.
15.
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Köster O, Büttner T. Diagnosis and monitoring of middle
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transcranial color-coded real-time sonography in patients
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Seward JB. Second harmonic imaging of an intravenously
administered echocardiographic contrast agent.
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17.
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initial exposure to diagnostic ultrasound pressures with
minute doses of intravenously injected microbubbles:
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19.
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© 1998 American Heart Association, Inc.
Original Contributions
Transient Response Harmonic Imaging
An Ultrasound Technique Related to Brain Perfusion
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and
Purpose—Gray-scale harmonic imaging is the first method to
visualize blood perfusion and capillary blood flow with ultrasound
after intravenous contrast agent application. The purpose
of the present study was to evaluate the potential of transient
response second harmonic imaging (TRsHI) to assess normal echo contrast
characteristics in different brain areas by transcranial
ultrasound.
Key Words: echocardiography • imaging, harmonic • imaging, transient response • perfusion, brain • ultrasonography, Doppler, transcranial
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The clinical utility of ultrasound contrast agents is
limited by the poor performance of currently available B-mode
scanners at discriminating echogenic microbubbles in the blood pool
from the surrounding echogenic tissue. Harmonic imaging (HI) is a new
contrast-specific imaging modality that uses the nonlinear properties
of ultrasound contrast agents by transmitting at the fundamental
frequency and receiving at multiples of this
frequency.1 2 The first multiple of the
fundamental frequency is generally the strongest of all possible
harmonic frequencies (second harmonic imaging
[sHI]).3 4 The major advantage of this
technique is due to the difference in backscattering of the tissue and
contrast agent at 2 frequencies. The magnitude of the backscattered
contrast-enhanced signal at the harmonic frequency is greater than that
of tissue, which leads to a significant increase of the signal to noise
ratio. The nonlinearity of the ultrasound contrast agent allows
capillary blood flow to be separated from tissue
echos.1 In this way sHI may clearly enhance the
ability of B-mode scanners to differentiate bubbles in the tissue
vascular space from the relatively echogenic surrounding avascular
tissue. Three preliminary studies have demonstrated the potential
clinical value of this technique in the assessment of myocardial
perfusion in humans5 6 and liver
perfusion7 in animal models. Furthermore, a HI
study in echocardiography has demonstrated that
visually detectable myocardial perfusion is especially accentuated when
the time interval between triggered frame rates is extended to once
every 4 to 10 cardiac cycles (transient response [TR]
imaging).6 This modification of the frame rate
prevents the destruction of microbubbles and has been shown to
significantly increase peak intensity (PI) of perfused
tissues.8 The present study evaluates whether
transient response second harmonic imaging (TRsHI) allows demonstration
of cerebral contrast enhancement in individuals without cerebrovascular
diseases.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Subjects
This study included 18 patients (mean age, 39 years; range, 22
to 56 years; 8 men, 10 women) without history or physical signs
of cerebrovascular disease. The exclusion criterion was galactosemia.
Informed consent was obtained from all individuals. Patients had the
following diagnoses: tension type headache (n=5),
polyneuropathy (n=5), radicular pain (n=2), trigeminal
neuralgia (n=2), psychogenic headache (n=2), myasthenia (n=1), and
myopathy (n=1). Extracranial and intracranial color-coded and spectral
Doppler examinations were normal in all individuals. In 10 patients
CT or MRI was performed and revealed no abnormalities.
For all ultrasound examinations, a Hewlett Packard SONOS 5500
duplex device capable of fundamental imaging and TRsHI in connection
with a 2.5-MHz, 90-degree sector transducer was used. We first
performed conventional transcranial gray-scale and
color-coded real-time sonography using the transtemporal
approach according to previously published
studies.9 A low insonation depth (10 cm) was
selected to improve the spatial resolution of parenchymal structures of
the ipsilateral hemisphere. The butterfly-shaped mesencephalic brain
stem with surrounding hyperechogenic basal cisterns was visualized in
axial untilted sections. For depiction of the third ventricle and the
thalamus, the ultrasound probe was tilted 
10 degrees toward the
parietal lobe. This plane of section was kept constant during the
entire TRsHI examination. The second harmonic system operated at
1.8-MHz transmit and at the second harmonic frequency of 3.6 MHz. The
instrument setting was not changed during the examination. The
ultrasound frame rate was switched to once every 4 cardiac cycles. A
400 mg/mL concentrated suspension of galactose-based microbubbles
(Levovist, Schering AG) (6.5 mL) was injected over a period of
10 seconds. This echo contrast agent exhibits a narrow distribution in
the range of microbubble size and is considered suitable for
reproducible backscatter measurements.10
Furthermore, a standardized injection technique was used to reduce
differences in the quality of the echo contrast agent to a minimum. All
preparations and injections of the microbubbles were performed by the
same investigator. In all examinations the echo contrast agent was
injected within 30 seconds after the end of the preparation into a
venous access with a standardized size (18 gauge) and localization
(antecubital vein). From the start of the injection the examination was
stored on magnetic optic disk over a period of 244 cardiac cycles (61
images). Thirty minutes later the examination was repeated on the
contralateral side. Quantitative measurements of parenchymal contrast
during the recorded examination period were performed off-line by
calculating gray-scale intensities of the integrated backscatter from
digital unprocessed data in defined regions of interest (ROIs). If
necessary, images were manually aligned before analysis of
optic intensity to correct for patient or ultrasound probe motions. A
time-intensity curve was created for the following circular ROIs on
both sides: (1) posterior part of the thalamus adjacent to the third
ventricle (ROIa) (diameter, 0.6 cm); (2) anterior part of the thalamus
adjacent to the third ventricle (ROIb) (diameter, 0.6 cm); (3) directly
adjacent to the thalamus (corresponding to the region of the lentiform
nucleus) (ROIc) (diameter, 1.2 cm); and (4) directly lateral to ROIc
(corresponding to the white matter) (ROId), (diameter, 1.2 cm). 
. The size of all ROIs was kept constant
in all measurements. The ratio of characteristic contrast curves
(baseline phase, phase of sudden increase of optic intensity to a peak
level, slow washout phase) was evaluated for each ROI. Background optic
intensity was subtracted by adjustment of the time-intensity curve to
the baseline before echo contrast enhancement. For quantitative
analysis, the following parameters were calculated
for each ROI: (1) area under the time-intensity curve (AUC)
(decibelsxcardiac cycles); AUC in TRsHI represents the total
intensity increase in gray-scale images in defined ROIs during the
entire examination caused by the echo contrast agent; (2) level of PI
(decibels); PI represents the maximal intensity increase in
gray-scale images in defined ROIs at 1 time point caused by the echo
contrast agent; and (3) time to PI from the start of echo contrast
application (cardiac cycles).
View larger version (127K):
[in a new window]
Figure 1. Transtemporal axial diencephalic plane
of section with ultrasound probe shifted toward the parietal lobe.
th indicates thalamus; a through d, ROIs: a, posterior part of
thalamus; b, anterior part of thalamus; c, region of the lentiform
nucleus; and d, region of white matter.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
General
All patients had adequate acoustic bone windows, enabling
visualization of the third ventricle and the thalamus in
transcranial real-time images. When the second harmonic
mode was used the structural components of the B-mode image were
preserved, albeit at a lower intensity. Thirty-six
intravenous injections of galactose-based microbubbles were
given; no side effects could be observed. Three characteristic phases
of contrast enhancement could be visually observed in all subjects.
After a baseline period of 10 cardiac cycles (phase 1), gray-scale
intensity (particularly in ROIc and ROId) increased to a maximum within
a few cycles (phase 2), whereas anterior and posterior parts of the
thalamus exhibited only a minor intensity increase. In the third phase,
contrast enhancement slowly disappeared. This tiding effect was best
observable in those regions with most prominent contrast enhancement
during phase 2. An example for these characteristic phases is given in
Figure 2.
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[in a new window]
Figure 2. Contrast enhancement at different time points in
axial diencephalic gray-scale images. A, Before echo contrast
application: visualization of the third ventricle (arrow) and the
adjacent ipsilateral thalamus (T). B, Visible contrast appearing first
in projection to the lentiform nucleus (1) after 24 cardiac cycles.
C, Maximal contrast causing an increase in optic intensity in all ROIs;
contrast enhancement is most accentuated in projection to the
lentiform nucleus (1) and the white matter (2), with only moderate
increase of optic intensity in the region of the thalamus (3). D,
Disappearing contrast enhancement after 244 cardiac cycles; compared
with panel A, optic intensity in gray-scale images is still increased
in the region of the lentiform nucleus and the thalamus.
Data of all quantitative parameters are summarized
according to different ROIs in Tables 1 to 4.
Figure 3 demonstrates typical
time-intensity curves in the ROIs. Characteristic time-intensity
contrast curves that allowed quantitative analysis were evident
in 32 of 36 examinations of ROIc and ROId on the left side and in all
examinations of ROIc and ROId on the right side. Four curves in ROIa (3
on the left, 1 on the right side) and 5 curves (4 on the left, 1 on the
right side) in ROIb could not be assessed because of insufficient
contrast enhancement. Peak enhancement in ROIa was observed 24 to 88
cardiac cycles after the injection of the contrast agent. For the other
ROIs the time intervals varied between 24 and 60 (ROIb), 20 and 76
(ROIc), and 20 and 80 (ROId) cardiac cycles, respectively. In ROIc and
ROId, high AUCs (all in decibelsxcardiac cycles) (404 to 2334 in ROId;
145 to 5160 in ROIc) could be observed. Highest AUCs in ROIa and ROIb
were 1249 and 1264, respectively. PI ranged between 0.4 and 7.6 dB for
ROIa, 0.8 and 17.6 dB for ROIb, 3 and 54.6 dB for ROIc, and 2.7 and
32.6 dB for ROId. AUCs in ROIc and ROId were significantly elevated
compared with ROIa and ROIb (each P<0.0001).
View this table:
[in a new window]
Table 1. Quantitative Analysis of Posterior Part of Thalamus
(ROIa) in 18 Patients
View this table:
[in a new window]
Table 2. Quantitative Analysis of Anterior Part of Thalamus
(ROIb) in 18 Patients
View this table:
[in a new window]
Table 3. Quantitative Analysis of Lentiform Nucleus (ROIc) in
18 Patients
View this table:
[in a new window]
Table 4. Quantitative Analysis of White Matter (ROId) in
18 Patients
View larger version (113K):
[in a new window]
Figure 3. Time-intensity curves in different ROIs: A,
posterior part of thalamus; b, anterior part of thalamus; C, lentiform
nucleus; and D, white matter. All curves show a characteristic
baseline phase before contrast enhancement (phase 1), a sudden increase
of contrast enhancement causing the peak intensity (phase 2), and a
slow washout phase (phase 3). Note the higher PIs and AUCs (different
values on the y axis) for the lentiform nucleus and the
white matter compared with the thalamus.
Side differences (>2-fold increase of PI or AUC in all ROIs on 1
side compared with the contralateral side) could be found in 3
individuals (patients 8, 9, and 11). In all those examinations the
right-sided ROIs were elevated compared with the left side. In the
remaining 15 subjects, 46 of 49 ROIs that could be evaluated had a
<2-fold side difference with respect to the AUC. In 1 subject ROIa and
ROIc demonstrated a >2-fold AUC side difference; in another individual
ROIa demonstrated a >2-fold AUC side difference.
Detailed data about all AUC ratios are summarized in Table 5. AUCc/a, AUCc/b, and AUC d/b were >2
in all examinations; AUCd/a was >2 in 28 of 30 examinations. In 13
(c/a), 13 (d/a), 15 (c/b), and 13 (d/b) investigations, AUC ratios were
>5. In a comparison of AUC ratios of the left and right sides, none of
the subjects, including those (patients 8, 9, and 11) with marked side
differences in absolute AUC values, showed a >2-fold difference when
any ratio was considered. There was no significant difference between
right and left examination side in AUC ratios in any ROI.
View this table:
[in a new window]
Table 5. Ratios of AUCs of Different ROIs
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Ultrasound contrast agents producing enhancement of the
backscattered ultrasound signal are of increasing interest in
neurosonology.11 12 13 Recently published studies
have shown their diagnostic potential in cerebrovascular
disease.14 15 However, all
transcranial echo contrast studies concentrated on the
assessment of intracranial vessels of the circle of Willis in
conventional color-coded images. In contrast, harmonic ultrasound is an
approach that exploits the nonlinear resonance of microbubbles when
exposed to an acoustic field, allowing enhanced detection of
contrast-containing parenchymal and vascular structures while
suppressing the reception of echoes from noncontrast-containing
structures.16 In the field of neurosonology, 1
preliminary color-coded HI study on the assessment of vessels of the
vertebrobasilar system has been published.17 The
authors found that the diagnostically useful period could
be prolonged by HI. Fundamental frequency and echo contrast
concentration identical to those in our study were used. Furthermore,
spatial resolution was improved compared with conventional color-coded
images, enabling visualization of more arterial and venous
vascular structures. 4 minutes. Another limitation with
triggering frame rates is that patient and transducer motions can
scarcely be corrected during the examination. Modified frame rates (eg,
once every cardiac cycle) can shorten the examination period and
improve anatomic orientation.
Acknowledgments
The authors wish to thank Hewlett Packard Laboratories/Germany
for the provision and maintenance of the ultrasound system. We
are indebted to Andre Steinbrink and Gudrun Pajain (Hewlett Packard)
for technical assistance in the study.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Forsberg F, Goldberg BB, Liu JB, Merton D, Rawool
M. On the feasibility of real-time, in vivo harmonic imaging with
proteinaceous microspheres. J Ultrasound Med. 1996;15:853–860.[Abstract]
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S. H. Meves, W. Wilkening, T. Thies, J. Eyding, T. Holscher, M. Finger, G. Schmid, H. Ermert, and T. Postert Comparison Between Echo Contrast Agent-Specific Imaging Modes and Perfusion-Weighted Magnetic Resonance Imaging for the Assessment of Brain Perfusion Stroke, October 1, 2002; 33(10): 2433 - 2437. [Abstract] [Full Text] [PDF]
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J. U. Harrer and C. Klotzsch Second Harmonic Imaging of the Human Brain: The Practicability of Coronal Insonation Planes and Alternative Perfusion Parameters Stroke, June 1, 2002; 33(6): 1530 - 1535. [Abstract] [Full Text] [PDF]
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 G. Deklunder Role of ultrasound and contrast-enhanced ultrasound in patients with cerebrovascular disease Eur. Heart J. Suppl., March 1, 2002; 4(suppl_C): C51 - C55. [Abstract] [PDF]
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 S.-J. Rim, H. Leong-Poi, J. R. Lindner, D. Couture, D. Ellegala, H. Mason, M. Durieux, N. F. Kassel, and S. Kaul Quantification of Cerebral Perfusion With "Real-Time" Contrast-Enhanced Ultrasound Circulation, November 20, 2001; 104(21): 2582 - 2587. [Abstract] [Full Text] [PDF]
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J Federlein, T. Postert, S Meves, S Weber, H Przuntek, and T. Buttner Ultrasonic evaluation of pathological brain perfusion in acute stroke using second harmonic imaging J. Neurol. Neurosurg. Psychiatry, November 1, 2000; 69(5): 616 - 622. [Abstract] [Full Text] [PDF]
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M. Wiesmann and G. Seidel Ultrasound Perfusion Imaging of the Human Brain Stroke, October 1, 2000; 31(10): 2421 - 2425. [Abstract] [Full Text] [PDF]
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C. Pohl, K. Tiemann, T. Schlosser, and H. Becher Stimulated Acoustic Emission Detected by Transcranial Color Doppler Ultrasound : A Contrast-Specific Phenomenon Useful for the Detection of Cerebral Tissue Perfusion Stroke, July 1, 2000; 31(7): 1661 - 1666. [Abstract] [Full Text] [PDF]
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G. Seidel, C. Algermissen, A. Christoph, T. Katzer, M. Kaps, and R. W. Baumgartner Visualization of Brain Perfusion With Harmonic Gray Scale and Power Doppler Technology : An Animal Pilot Study Editorial Comment: An Animal Pilot Study Stroke, July 1, 2000; 31(7): 1728 - 1734. [Abstract] [Full Text] [PDF]
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G. Seidel, C. Algermissen, A. Christoph, L. Claassen, M. Vidal-Langwasser, and T. Katzer Harmonic Imaging of the Human Brain : Visualization of Brain Perfusion With Ultrasound Stroke, January 1, 2000; 31(1): 151 - 154. [Abstract] [Full Text] [PDF]
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T. Postert, J. Federlein, S. Weber, H. Przuntek, and T. Buttner Second Harmonic Imaging In Acute Middle Cerebral Artery Infarction : Preliminary Results Stroke, August 1, 1999; 30(8): 1702 - 1706. [Abstract] [Full Text] [PDF]
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