From Lille University Hospital (G.D., J.-L.L., C.G.) and Charles De
Gaulle University (M.R.), Lille, France.
Correspondence to Dr G. Deklunder, EFCV, Hôpital Cardiologique, CHU de Lille, av du Pr. Leclerc, F-59037 Lille Cédex, France. E-mail gdeklunder{at}chru-lille.fr
Methods—Three groups of 12 volunteers each were composed of
patients with an MHV and embolic signals in the cerebral circulation
(group 1), patients with biological prostheses (group 2), and healthy
subjects (group 3). Groups were carefully matched for age and verbal
intellectual abilities. For each group, a transcranial
Doppler examination was performed and a set of cognitive tests
assessing sustained and selective attention and episodic and working
memory was administered.
Results—The mean embolic rate was 29 per hour in patients with an
MHV. No embolus was detected in the other 2 groups. Episodic memory was
significantly modified in both groups 1 and 2 compared with the control
group for tasks that required high-processing resources. Working memory
performance was significantly decreased in MHV patients. No
between-groups differences were observed for the other
parameters.
Conclusions—Alteration of episodic memory can be attributed to a
long-term effect of the surgical procedure. Deterioration of working
memory can be related to the presence of cerebral microemboli in MHV
patients.
The nature of HITS in patients with a normal MHV is still being
debated, but there are strong arguments in favor of a gaseous origin:
microbubbles can be produced at the level of the valve leaflets where
local high-pressure gradients are present during the cardiac cycle,
especially at valve closure. These pressure gradients could lead to the
appearance of a cavitation-like phenomenon that can release part of the
dissolved blood gas under the form of microscopic bubbles into the
circulation.6 7 8
Circulating microbubbles have been reported in other circumstances, eg,
during coronary artery bypass
grafting.9 10 A decline in cognitive
performances of these patients has been reported, and its
amplitude has been correlated to the amount of gas emboli delivered
during the extracorporeal circulation (ECC). The consensus is
increasing that diffuse microembolization, secondary to ECC, is the
primary cause of cerebral damage in any uncomplicated open heart
surgery.11 12 13 In divers, central nervous system
damage has been reported using magnetic resonance
imaging.14 Moreover, a direct deleterious effect
of gaseous microembolization has been demonstrated on the cerebral
microvasculature.15 16
These observations were made during situations of acute embolization.
Although most of the chronic emboli in patients with an MHV are
clinically silent, it is reasonable to assume that such repeated events
could have subtle cumulative effects on the cerebral microcirculation
and thus on some cerebral functions.
The presence of memory and attention disorders is frequently reported
in patients with brain damage and particularly after open heart
surgery.17 18 As in previous studies conducted on
patients after cardiac surgery, the present study was designed to
assess attention and memory of patients with MHV-associated HITS.
Neuropsychological procedures were selected on the basis of their use
in previous studies.
Sustained attention and selective attention were the 2 types of
attention explored in this study. The assessment of short-term memory
was investigated with regard to the working memory model of
Baddeley.19 This model refers to a limited
capacity system that is responsible for the temporary storage and
processing of information while cognitive tasks are being performed.
Long-term memory performance was assessed by testing the
episodic memory,20 which concerns facts of
personal experience.
A specifically designed battery of neuropsychological tests has been
used to explore the sustained and selective attention and the working
and episodic memory. This battery of tests was applied to (1) a group
of patients with an MHV and repeatedly occurring HITS, (2) a group of
patients having undergone a similar cardiac surgery procedure with
implantation of a biological valve, and (3) a group of healthy
subjects. These last 2 groups did not present any HITS.
Eligible subjects were tested for inclusion criteria and group matching
on entry in the study. Thirty-six subjects met the inclusion and
pairing criteria and were then assigned to 1 of 3 groups according to
their heart valve status: group 1, 12 patients with 1 or 2 MHVs
implanted and exhibiting HITS in both the left and right MCA; group 2,
12 patients with a biologic heart valve implanted and presenting no
HITS; and group 3, 12 healthy control subjects, with no prostheses.
The noninclusion criteria were defined to eliminate cerebrovascular
risk factors and neurological and psychological disorders. Patients
with prior history of stroke, multiple sclerosis, vascular disorders
with possible cerebral affection, diabetes mellitus, general
psychiatric disorders, illiteracy, and pharmacological treatment known
to interfere with cognitive performance were excluded on the
basis of a neurological examination. Patients were then submitted to
clinical and echographic cardiac examinations to exclude patients with
arrhythmia, hypertension, cardiac insufficiency,
dysfunction of the prosthesis, or presence of any other cardiac
embolic source. Duplex carotid examination was performed to exclude
subjects with significant carotid atheroma (>70%
stenosis or heterogeneous and irregular plaques),
which is the most common extracardiac source of cerebral
microemboli.21 Blood tests were performed on MHV
patients to ensure the efficiency of anticoagulation therapy. Patients
with an international normalized ratio <3 were excluded. Because
anxiety may affect neuropsychological performance, the anxiety
test of Catell22 was administered to all
subjects, and they were excluded if their scores reached the
pathological anxiety level.
Patients in group 1 had a St. Jude prosthesis (St. Jude
Medical, Inc) implanted in either the mitral (5 subjects) or the aortic
position (5 subjects) or in both the mitral and aortic positions (2
patients). Mean time from implantation was 32 months (range 12–76
months). The prosthesis size ranged from 27 to 31 in the mitral
position and from 21 to 25 in the aortic position.
Patients of group 2 had a Carpentier-Edwards prosthesis
(Baxter Inc) implanted in the mitral position (7 subjects) or a
Carpentier-Edwards prosthesis (2 subjects) and a
Toronto SPV prosthesis (St. Jude; 3 subjects)
implanted in the aortic position. Mean time from implantation was 39
months (range 18–88 months).
Subjects in the 3 groups were matched for age and verbal intellectual
abilities obtained by administering the vocabulary subtest of the
Wechsler Adult Intelligence Scale-Revised
(WAIS-R).23 This test estimates the global
intellectual function that is not expected to change after a cardiac
operation. Basic clinical and neuropsychological data are provided in
Table 1
Microemboli Detection
The gain of the spectrum analyzer was set up to a low value to
obtain a background Doppler signal within a few color levels. The
criteria used for the HITS detection were those originally proposed by
Spencer1 characteristic chirping sound, initially
unidirectional signal in the Doppler spectrum, random appearance
within the cardiac cycle, and intensity increase
Cognitive Tests
Selective-attention abilities were assessed by a sign-crossing task. A
sheet with 500 meaningless, randomized, mixed-up signs was
presented to each subject. Three signs placed at the top of the
sheet were designed as targets. The subject was asked to scan the sheet
as quickly as possible, keeping errors to a minimum, and to cross the
target signs each time he or she found one of them. The time used to
complete the task was measured as well as the number of correct
responses (targets crossed) and false alarms (nontargets crossed).
Focused attention and inhibition abilities were assessed using an
adaptation of the Stroop24 color task. In this
task, a list of words printed in colored ink was presented to
each subject. First, he or she was asked to read the list of words as
quickly and accurately as possible. The time to read the list and the
number of reading errors were counted. Afterward, each subject was
asked to name the color of ink in which the word was presented.
The time to name the colors and the number of naming errors were
counted. Interference was evidenced by the time ratio of the 2 parts of
the task: time to name the colors/time to read the words.
Memory
Episodic memory was also tested by using an adaptation of the paradigm
of Smith and Milner.26 The subject named and
evaluated the price of 16 miniature articles representing
real-life objects (eg, chair, chest, bottle of milk); the subject was
instructed that a recall of the articles would be asked later.
Afterward, the subject was asked to recall most of the previously
presented articles. A recognition stage was performed in which
the subject was presented a list of 48 words, including the
name of the 16 learned articles among 32 distractors. Each word was
read to the subject who had to indicate whether or not the article was
in the ones presented. Performance was assessed by the
number of items correctly recalled during the recall task and the
number of correct and false recognitions during the recognition task.
The visuospatial working memory task was assessed using a modified
version of the task developed by Peterson and
Peterson.27 The subject was presented
with 3 visual meaningless signs that had to be recognized after a delay
(7 seconds), during which he or she was distracted by a subsidiary
task. The subsidiary task consisted of counting backward by
sevens during 7 seconds from a random number given orally by the
examiner. At the beginning of the procedure, practice trials were
administered to familiarize the subject with the test. The subject was
tested on 12 trials. The dependent variables were the number of
correct recalls and the number of false recognitions.
Data Analysis
Intellectual level assessed by the WAIS-R with the vocabulary and
digital symbol subtests did not significantly differ among the 3
groups: (F2,33=0.04, P=NS),
(F2,33=0.66, P=NS), and
(F2,33=0.42, P=NS), respectively
(Table 1
Attention Evaluation
Memory Evaluation
Working Memory
HITS are commonly reported in the cerebral circulation of
patients with MHVs.3 5 The embolic signals
recorded from these patients have been described as being more
intense than those found in patients with other potential embolic
sources2 36 and thus are likely to be due to
large solid emboli or gaseous bubbles that have a high-ultrasound
reflectivity. Several arguments have been made in favor of a gaseous
origin of HITS associated with MHV and have been previously
discussed.6 Among these arguments, the lack of
relationship between the degree of anticoagulation, antithrombotic, or
antiplatelet therapy and the HITS rate must be
highlighted.37 38 39 Moreover,
microembolic signals are not observed in normally
functioning biological valves.40 A low HITS rate
has however been reported in patients with biological prostheses. It
must be stressed that in these reports there was no valve nor carotid
control, and the microemboli observed could be of a solid
nature.4 41
It can be assumed that microbubbles are generated by the sharp MHV
motion, creating a local, transient, high-pressure gradient that may
cause a cavitation-like phenomenon, especially during closure, as
demonstrated in vitro.8 Microbubbles can survive
in the vessels, as demonstrated by decompression
follow-up28 or detection of echo contrast agents
far from the injection site,42 and therefore can
be detected in the arteries, downstream to the prosthesis.
From the literature, it seems that some cognitive abilities are
impaired in up to two thirds of patients in the early stages after
coronary artery bypass grafting compared with the preoperative
status.18 The origin of the cerebral injury after
cardiac surgery is probably multifactorial and is still being
debated,43 because the neuropsychological
impairment observed in open heart patients can be caused by both the
severe preexisting cardiac disease and the cardiac surgical procedure
itself. However, the cause seems mainly related to prolonged or severe
hypoperfusion and to gaseous emboli from the bypass
circuit.11 12 The cognitive impairments are
reversible in some patients but not in others, in whom impairment still
can be observed 2 months17 or 6
months44 later. The cognitive impairment severity
seems to be causally related to the bypass duration and the number of
microemboli delivered during surgery.10 Because
gaseous microemboli delivered during the course of a few hours
(duration of surgery) are able to induce some transient or even
persisting neuropsychological alterations, it may be hypothesized that
the chronic microembolization occurring in patients with an MHV can
induce comparable effects. These neurological effects are possibly
related to the memory complaints reported by the patients with an
MHV.
The present study was designed with 2 control groups. A true
control group was composed of healthy subjects to obtain reference
values; this is mandatory when nonstandard neuropsychological tests are
used and when normative data are not available. The second control
group was composed of patients with a biological valve
prosthesis implanted. These subjects underwent a similar
surgical procedure compared with the subjects who had an MHV implanted.
Moreover, the preoperative medical history and disease were similar for
the patients of these 2 groups. The formation of the second control
group was necessary because it is difficult to have a group of patients
with an MHV and free of HITS, whereas most patients with normal
biological prostheses do not exhibit HITS.40 This
design was expected to discriminate the effects of surgery and
microembolization from MHV.
Time from implantation was of similar length in the 2 surgical groups
(mean time 32 and 39 months in groups 1 and 2, respectively). It can be
assumed that the long-term effect of ECC on cognitive functions was
similar in both groups 1 and 2. However, the 2 groups differ after
surgery: patients in group 1 showed HITS in their cerebral circulation
from implantation whereas patients included in group 2 did not show any
HITS. It has been demonstrated that the embolic rate is stable for 1
year in MHV patients (50 patients with St. Jude prostheses, G.
Deklunder, unpublished data, 1994; Reference 4545 ). Group 1 of the
present study consisted of patients who experienced a stable,
repeated microembolization for 12 to 76 months.
The neuropsychological tests used in this study concern the cognitive
abilities that are likely to be affected after cardiac
surgery,46 47 eg, psychomotor speed, attention,
and new learning abilities. Parts of these tests derived for the
present study have been described in the experimental cognitive
literature.
Contrary to previous postcardiac surgery studies, a decrement in
attentional performance was not found in the present study
nor was there a slowing of patient responses in the reaction time test.
It must be emphasized that the reaction time test used in the
present study involved only simple stimuli and simple motor
responses whereas other investigators have used reaction time tests
involving more complex cognitive processes.17 The
discrepancy between the results then can be attributed to different
memory loads or different general difficulty levels of the tasks.
Nevertheless, because the time of the postoperative testing interval is
longer than in the previous studies (32 months), the observed normal
attentional performance could be due to a progressive
reversibility of the impaired process. Otherwise, this reversibility
implies that the brain aggression provoked by the acute
microembolization during ECC and the chronic microembolization produced
by an MHV is of a different nature.
For episodic memory, a lower performance was observed in the 2
groups of patients with prosthetic valves implanted but only as
assessed with the procedure of Smith and
Milner.26 In this paradigm, the subjects must
name the presented objects and evaluate the price. Thus, the
encoding process is double (visual and verbal) and deeper compared with
the 12-word list test. In healthy control subjects, this encoding
process resulted in a higher percentage of recalled items in the
paradigm of Smith and Milner compared with the 12-word list test. On
the contrary, patients with prosthetic valves implanted
performed worse and did not seem to benefit from the deeper encoding
process. The difference between the results in controls and patients
could be interpreted as a difference in encoding strategy. Therefore,
the long-term memory impairment observed in the 2 groups of patients
with prosthetic valves could be attributed to a common surgical
event that is probably an ECC effect.
The task of Peterson and Peterson27 used in the
present study has been shown to be highly sensitive to the effects
of brain injury.48 The results obtained with this
task point out a short-term memory deficit in the patients with an MHV
whereas patients with biological valves and controls present
comparable performance. Because of time constraints for the
subjects, the design of the neuropsychological test battery did not
address all the subsystems of the short-term memory defined in the
model of Baddeley.19 Consequently, it is not
possible to adequately identify the specific components of the model
that may be affected by the presence of an MHV prosthesis.
Whatever the exact mechanism, this impairment has an important clinical
implication because it could be related to the presence of repeated
microemboli in patients with an MHV. It must be stressed that
microemboli production is causally related to the mechanical
properties of the prosthesis and that its prevalence is high in
any type of commercially available mechanical valve.
Nevertheless, the small size of the groups in the present study
does not allow for definite conclusions and does not yield the
possibility of determining a relationship between the HITS rate and the
degree of cognitive impairment. A serial study that is based on this
experiment and that uses a refined battery of tests is currently being
conducted to analyze the cumulative effects of microemboli on
brain morphology and cognitive functions and to specify the components
of the Baddeley19 memory model that are
affected.
Received February 13, 1998;
revision received May 25, 1998;
accepted June 26, 1998.
© 1998 American Heart Association, Inc.
Original Contributions
Microemboli in Cerebral Circulation and Alteration of Cognitive Abilities in Patients With Mechanical Prosthetic Heart Valves
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—It has
been shown previously that cerebral microemboli may occur frequently in
patients with a normal mechanical heart valve (MHV) without prior
history of stroke. Some arguments strongly suggest that these
microemboli have a gaseous origin. In other circumstances such as
extracorporeal circulation or decompression in divers, it has been
demonstrated that cerebral microbubbles could lead to some
deterioration in cognitive functions. Therefore, we have studied
attention and memory, which are among the most impaired cognitive
functions as demonstrated in previous studies, in patients with an
MHV.
Key Words: heart-valve prosthesis • HITS • cognitive abilities • transcranial Doppler
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Most patients who have a mechanical heart valve (MHV)
prosthesis implanted exhibit high-intensity transient signals
(HITS) in the cerebral circulation that are usually detected by a
transcranial Doppler examination of the middle cerebral
artery (MCA).1 The prevalence of HITS is high,
from 50% to 100% according to some studies,2 3 4 5
and thus it has an important clinical and economic effect considering
the high number of MHVs implanted in patients each year worldwide. In
view of this population, the rate of HITS widely varies according to
the prosthesis type, size, and status. However, the presence of
HITS is also observed in patients with normally functioning MHVs and
without other embolic source. In any case, the HITS rate can reach
several hundreds per hour.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Subjects
Patients were randomly selected from those regularly attending
Lille University Hospital who also met the inclusion criteria. Control
subjects were recruited by announcement, and the data obtained from
this group were used as reference values for the neuropsychological
tests. All subjects were informed about the study protocol and gave
consent to enter the study. 
.
View this table:
[in a new window]
Table 1. Clinical and Psychological Data of
Subjects
Each subject was submitted to a transcranial
sonographic examination of the left and right MCA, with the use of
Acuson 128XP equipment (Acuson) and a 2-MHz sector scanning
probe. The transcranial Doppler study was performed in
the pulsed Doppler mode, with the guidance of color Doppler
imaging. The MCA was imaged through the temporal acoustic window. The
sample volume of the pulsed Doppler was placed in the first segment
of the vessel, at approximately 50 mm deep; its length was 5
mm. Real-time spectrum analysis of the Doppler signal was
continuously recorded for 10 minutes on each side. The Doppler
spectrum and audio signals were recorded on videotape and
analyzed off-line by an independent observer who was blinded to
the clinical status of the subjects. 
10 dB above the
background spectrum. The embolic rate was determined by counting the
number of HITS during the recording period (20 minutes).
Results were reported as the number of events per hour.
Attention
Sustained-attention abilities were evaluated by a simple visual
reaction time test with 100 stimuli. The visual stimulus was a red
spotlight presented until the subject responded by depressing a
button with his or her index finger. The subjects were told to
respond as quickly as possible. At the beginning of the procedure,
practice trials were administered to familiarize the subjects with the
test. Reaction time was measured after each response. At the end of the
task, the mean reaction time was computed.
Episodic memory was assessed by asking the subject to learn and
recall a 12-word list.25 The words were read to
the subject at a rate of 1 word every 2 seconds. Immediately after this
reading, the subject was asked to recall the words. The number of
correct recalls and intrusions was counted. Ten minutes after the free
recall, a recognition task was performed. A list of 36 words containing
the 12 target words among 24 distractors was presented to the
subject; for each word, he or she was asked to say whether or not the
word was learned earlier. The number of correct and false recognitions
was counted.
Data were analyzed using a 1-way ANOVA with a post hoc
Student t test to compare the cognitive abilities of the 3
groups. A P value <0.05 was considered statistically
significant. Values are reported as mean±SD.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The mean HITS rate of patients in group 1 was 29 per hour (range
12–60 per hour). There was no significant difference in HITS rate
between the left or right MCA (mean paired difference=1.3±1.8).
No HITS were observed in groups 2 and 3. 
). The results of the cognitive tests are presented in
Table 2 for each group.
View this table:
[in a new window]
Table 2. Scores for Reaction Time, Sign-Crossing Test, Stroop
Color Test, and Episodic Memory and Working Memory
Tasks
There was no significant difference between the 3 groups
concerning the simple reaction time (F2,33=0.071,
P=NS). The number of correct responses and false alarms was
not significantly different across groups for the sign-crossing task
(F2,33=0.35, P=NS;
F2,33=0.72, P=NS). The time required
for the task completion did not significantly differ across groups
(F2,33=0.19, P=NS), and no significant
difference was found for the Stroop24
interference task (F2,33=0.07, P=NS).
Episodic Memory
There was no significant difference between groups for the free
recall of the 12-word list (F2,33=1.55,
P=NS), the number of correct recalls
(F2,33=2.17, P=NS), or the number of
false alarms in the recognition task (F2,33=2.43,
P=NS). However, there was a significant difference between
groups for correct recalls (F2,33=16.95,
P<0.05), with a lower performance in groups 1 and 2
compared with the control group, as assessed by the paradigm of Smith
and Milner.26 Post hoc analysis showed
significant differences between groups 1 and 3
(t22=5.47, P<0.01) and between
groups 2 and 3 (t22=5.96,
P<0.05) but no differences between groups 1 and 2. The
recognition task did not differ across groups in the number of correct
responses (F2,33=1.36, P=NS) or false
alarms (F2,33=2.57, P=NS).
There was a significant difference between groups in the number of
correct responses for the working memory task
(F2,33=4.13, P<0.05), with a lower
performance in group 1 (Table 2). Post hoc analysis
showed that the performance in group 1 was lower compared with
group 2 (t22=2.26, P<0.05) and
the control group (t22=2.63,
P<0.05).
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Doppler ultrasonography has been used for years to
investigate gas bubbles in blood vessels under various
circumstances28 29 30 31 and more recently to detect
formed element emboli.32 33 In experimental
studies, it has been demonstrated that various embolic materials,
including fat, gas, and thrombus and platelet aggregates, can be
detected with ultrasonography.34 The power of
backscattered ultrasound depends, to a large extent, on the size and
acoustic impedance of particles in the blood. When circulating emboli
are either much larger, eg, formed emboli, or of greatly different
acoustic impedance, eg, gas microbubbles, than individual blood cells,
they result in an increased Doppler signal power that can be easily
detected, the so-called HITS.35 The embolic
events may occur, and HITS may be detected in different vascular
regions, depending on the location of the embolic source, and in any
vascular bed, if a cardiac source is concerned. However, special
attention has been focused on the cerebral circulation because stroke
is a major concern.
Acknowledgments
We thank K. Dujardin, PhD, Charles De Gaulle University, and O.
Godefroy, MD, PhD, Lille University Hospital, for valuable advice in
the design of this study and in the interpretation of the
results.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
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 S. Milo, E. Rambod, C. Gutfinger, and M. Gharib Mitral mechanical heart valves: in vitro studies of their closure, vortex and microbubble formation with possible medical implications Eur. J. Cardiothorac. Surg., September 1, 2003; 24(3): 364 - 370. [Abstract] [Full Text] [PDF]
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M. Perthel, S. Kseibi, A. Bendisch, and J. Laas The dynamic bubble trap reduces microbubbles in extracorporeal circulation and high intensity transient signals in the middle cerebral artery: a case report Perfusion, September 1, 2003; 18(5): 325 - 329. [Abstract] [PDF]
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D. G. Nabavi, J. Stockmann, C. Schmid, M. Schneider, D. Hammel, H. H. Scheld, and E. B. Ringelstein Doppler microembolic load predicts risk of thromboembolic complications in Novacor patients J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 160 - 167. [Abstract] [Full Text] [PDF]
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J. Laas, S. Kseibi, M. Perthel, A. Klingbeil, L'E. El-Ayoubi, and A. Alken Impact of high intensity transient signals on the choice of mechanical aortic valve substitutes Eur. J. Cardiothorac. Surg., January 1, 2003; 23(1): 93 - 96. [Abstract] [Full Text] [PDF]
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D. Georgiadis, A. Studer, R.W. Baumgartner, and H.R. Zerkowski Clinical relevance of microembolic signals in patients with prosthetic heart valves Eur. J. Cardiothorac. Surg., September 1, 2002; 22(3): 490 - 491. [Full Text] [PDF]
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J.C. de la Torre Alzheimer Disease as a Vascular Disorder: Nosological Evidence Stroke, April 1, 2002; 33(4): 1152 - 1162. [Abstract] [Full Text] [PDF]
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D. W. Droste, K. Kuhne, R. M. Schaefer, and E. B. Ringelstein Detection of microemboli in the subclavian vein of patients undergoing haemodialysis and haemodiafiltration using pulsed Doppler ultrasound Nephrol. Dial. Transplant., March 1, 2002; 17(3): 462 - 466. [Abstract] [Full Text] [PDF]
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D. Georgiadis, S. Braun, F. Uhlmann, G. M. Bernacca, W. J. Schulte-Mattler, S. Zierz, and H. R. Zerkowski Doppler microembolic signals in patients with two different types of bileaflet valves J. Thorac. Cardiovasc. Surg., June 1, 2001; 121(6): 1101 - 1116. [Abstract] [Full Text] [PDF]
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F. Rolle, J. Pengloan, M. Abazza, J. M. Halimi, M. Laskar, L. Pourcelot, and F. Tranquart Identification of microemboli during haemodialysis using Doppler ultrasound Nephrol. Dial. Transplant., September 1, 2000; 15(9): 1420 - 1424. [Abstract] [Full Text] [PDF]
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