transcranial sonography

2. Prof. Hani Hamed Dessoki, M.D.Psychiatry
Acting Dean, Faculty of Nursing
Prof. Psychiatry
Founder of Psychiatry Depart., Beni Suef University
Supervisor of Psychiatry Depart., El-Fayoum University
Treasurer of Egyptian Psychiatric Association
2020
Emerging role of Transcranial Ultrasound
in Psychiatry

3. ‫سيكاترى‬ ‫عيادة‬
‫للمريض‬ ‫سونار‬ ‫مطلوب‬
‫دماغه‬ ‫على‬ ‫سونار‬

4. Agenda
• What is Transcranial ultrasound?
• Why transcranial ultrasound
• Role of TCS in neurology
• Emerging role of TCS in psychiatry
• Limitations of TCS
• Take home messages

5. What is Transcranial ultrasound

6. Introduction
• Transcranial sonography (TCS) is a relatively
new neuroimaging method which displays
tissue echogenicity (intensity of reflected
ultrasound waves) of the brain through the
intact skull.
• TCS systems display deep echogenic brain
structures with a high image resolution which
is even higher than that of magnetic
resonance imaging (MRI).

7. • Transcranial sonography (TCS) is a non-invasive
and inexpensive neuroimaging method.
• The visualization of deep brain structures
through the intact skull via the bilateral
temporal.
• Acoustic bone windows.

9. • TCS of brain structures is performed through
the temporal acoustic bone window, with
preauricular position of the ultrasound probe
parallel to the orbitomeatal line.

10. • The ultrasound waves are reflected at tissue
interfaces depending on tissue density and
composition, resulting in differential
echogenicity of brain nuclei and the ventricular
system.
• In the last two decades TCS has become a
widely used diagnostic tool mainly in
neurological disorders.

11. • Different brain structures may be visualized in
distinct echogenic investigation planes resulting
from the modulation of the angle of the
ultrasound probe on the temporal bone window.
• Among them are the substantia nigra (SN), red
nucleus, brainstem raphe (BR), thalamus,
caudate nucleus (CN), lenticular nucleus (LN),
third ventricle, the lateral ventricle and its
frontal horn.

12. • The development of transcranial B-mode
sonography in the 1990s enabled clinicians to
visualize parenchymal structures and lesions
like brain tumours and hematomas.
• Another application of this technique is the
measurement of the ventricular system in
hydrocephalus or other diseases.

13. Role of TCS in Neurology
• Intracranial Steno-occlusive disease
• Stroke Prevention in Children and sickle cell
Disease
• Vasospasm in SAH
• Cerebral monitoring and micro-emboli
detection
• Diagnosis of RT to LT Shunt and PFO
• Sono-thrombolysis
• Diagnosis of Brain death

14. • The pioneering studies of Georg Becker in the
90’s provided insight into echogenic
alterations in psychiatric conditions , which
resulted in widespread research activities in
various psychiatric disorders such as
obsessive-compulsive disorder (OCD),
attention-deficit/hyperactivity disorder
(ADHD), schizophrenia, depression, bipolar
disorder (BD) and others.

15. Why Transcranial Ultrasound

16. Advantages of TCS
• Transcranial sonography (TCS) is a non-
invasive and inexpensive neuroimaging
method for the visualization of deep brain
structures through the intact skull via the
bilateral temporal acoustic bone windows.
• Applicability, even in moving (e.g. agitated)
patients.
• The fact that it is quick and repeatedly
performable with no limitations as known
from other neuroimaging techniques (metal in
the body as a limitation).

17. • TCS provides a way to visualize brain
structures in young populations without any
negative side effects Particularly in children
and adolescents, the use of invasive
techniques or imaging techniques entailing
radiation (e.g. PET) is a matter of ethical
debate

18. • Besides the specific finding of the substantia
nigra (SN) hyperechogenicity in Parkinson’s
disease (PD), first time described in 1995 by
Becker et al.
• Parenchymal structures that can be visualized
are the substantia nigra (SN), red nucleus,
brainstem raphe (BR), thalamus, caudate
nucleus (CN), lenticular nucleus (LN), third
ventricle, the lateral ventricle and its frontal
horn (Walter, et al. 2007).

19. Mesencephalic Plane

20. Thalamic Plane

21. Emerging role of TCS in psychiatry

22. TCS in unipolar depression
• Typical ultrasound marker that can be of value
in the diagnosis and differential diagnosis of
depression is the low echogenicity or
interrupted Brain stem Raphe .
• Raphe hypoechogenicity is a common finding
in 50—70%of patients with unipolar
depression. and is associated with
responsivity to serotonin-reuptake inhibitors
(SSRI).

23. • In the study which compared echogenicity
between 40 patients with unipolar depression,
40 patients with bipolar disorder and 40
healthy controls.
• Raphe echogenicity in patients with unipolar
depression was found to be distinctly reduced
as compared with healthy adults and patients
with bipolar affective disorder.

24. • Reduced brainstem midline echogenicity of
depressed patients was interpreted as a
structural alteration of the dorsal raphe
nucleus or fiber tracts in this region.
• Recently, reduced raphe echogenicity was
found in 47% of the patients with major
depressive disorder but only in 15% of healthy
controls.

25. • In patients with suicidal ideations that finding
was even more pronounced (86%) with the
highest frequency of completely not visible
TCS raphe finding 72 %

26. • These findings are in line with the results of
PET studies demonstrating morphological and
functional alteration of the dorsal raphe
nucleus in major depression, with decreased
serotonin type 1A receptor binding and fewer
neurons expressing serotonin transporter
mRNA compared with findings in controls.

27. It was suggested that these signal alterations
could reflect myelin-breakdown of pathways
running through the midline structure and
therefore cause this TCS and MRI phenotype
and point towards basal limbic alterations in
depression, a finding which was confirmed in a
preliminary post mortem investigation (Becker,
et al. 2001)

29. TCS in bipolar disorder
• Recently, Krogias et al. found the BR
hypoechogenicity in 36.1% of the 36 patients with
bipolar I disorder (14 depressed, 8 manic, 14
euthymic) and in 20% of the 35 healthy controls.
• Compared to the control group, frequency of
altered BR echogenicities did not reach statistical
significance.

30. TCS in bipolar disorder
• Hypoechogenicity of BR was found in six (42.9%) of
the depressed, in three (37.5%) of the manic and
in four (28.6%) of the euthymic bipolar patients,
with no significant difference between the three
subgroups .

31. • The width of third ventricle was significantly
larger in the patient group (3.8±2.1mm vs.
2.7±1.2 mm).
• Depressed bipolar patients with reduced BR
echogenicity showed significantly higher
scores on the Hamilton Depression Rating
Scale as well as the Montgomery-sberg
Depression Rating Scale .

32. Anxiety and OCD
• A pilot-study of 31 OCD patients has
demonstrated a tendency to reduced BR
echogenicity and a significantly increased
echogenicity of the Caudate Nucleus compared to
controls.
• The hyperechogenicity of the CN in OCD could
reflect a disease-specific alteration possibly due
to changes in the microarchitecture of the CN in
this disorder (Mavrogiorgou, et al. 2013).

33. • It is generally assumed that the functional
connectivity of the cortico-striato-
thalamocortical circuitry is affected in OCD
(Bernstein et al. 2016), especially the
decreased left CN-thalamus connectivity
(Chen, et al. 2016).
• increased iron deposition could also account
for the hyperechogenic phenotype of the CN,
as demonstrated with a MRI study in the basal
ganglia of OCD patients (Correia et al. 2010).

34. Panic disorders
• In a study in patients with panic disorder SN and BR
were evaluated with TCS (Silhan et al. 2015). BR
hypoechogenicity was detected more frequently in
patients compared to controls.
• No relationship was found between the BR and SN
echogenicities and the severity of panic disorder or
comorbid depression.

35. Schizophrenia
• Becker et al. investigated the BR in patients with
schizophrenia and found it comparable to
healthy controls (Becker, et al. 1995).
• Psychiatric patients who developed more severe
antipsychotic-induced parkinsonism (AIP) were
shown to have larger areas of SN
hyperechogenicity (Berg et al. 2001).

36. • Further exploring the relationship between SN size
and AIP (Jabs et al. 2003), the group found that age
and SN size predict AIP and correlate with its
severity.

37. • Investigations of SN hyperechogenicity in 62 never
treated schizophrenic patients, their 80 unaffected
first-degree relatives and 62 healthy controls, were
found more distinct in the schizophrenic group
compared to relatives and controls, associated with
stronger motor impairments, more pronounced in
males and in the right SN compared to the left side
(Kamis et al. 2015).

38. Autism Spectrum disorder
• In the sole TCS study on autism spectrum
disorder (ASD), Bradstreet et al. have not
examined midbrain structures but focused
instead on cortical architecture and extra-axial
fluid (EAF) (Bradstreet, et al. 2014)
• The finding of cortical dysplasia and increased
EAF in 23 patients is the only TCS study so far
in ASD

39. • Increased EAF has also been observed in an
MRI study in siblings of ASD children who
were subsequently diagnosed with ASD as
well, whereas siblings where EAF had
normalized by age 2 did not have an increased
risk of an ASD diagnosis (Shen et al. 2013).

40. • Cortical dysplasia was defined as intracortical
hypoechoic lesions or abnormal layering
within the cortical grey matter.
• EAF was quantified as the space between pia
mater and arachnoidea at the gyral summit.

41. • As a potential pathomechanism of the
increased EAF, the authors imply abnormal
immune system activation.
• Based on Theoharides and Zhang
(Theoharides and Zhang 2011) mast cells
interfering with the blood brain barrier raise
its permeability and thus disturb the
intracranial fluid pressure balance, and the
widening of the EAF is supposed to serve the
re-establishment of the fluid equilibrium.

42. ADHD
• To date, two studies employed TCS to examine the
SN in paediatric ADHD.
• Romanos and colleagues reported
hyperechogenicity of the SN in children aged 7-16
diagnosed with combined type ADHD (Romanos,
et al. 2010).

43. ADHD
• Another study included patients with combined
and inattentive subtype and a subclinical group.
• SN echogenicity was found to be increased in all
ADHD groups compared to controls regardless of
age and sex while the ADHD subgroups did not
differ among themselves

44. • SN echogenicity correlated with symptoms
of inattention, hyperactivity, and impulsivity,
but not oppositional or conduct disorder
symptoms (Krauel, et al. 2010).

45. Limitations of TCS

46. Limitations of TCS
• One of the major limitations is the
dependency on transcranial insonability,
with the bone window being insufficient in
5-20 % of Caucasian subjects (with elderly
having less sufficient bone windows) and
13.5 – 21 % in Asian populations.

47. • Cortical structures are thus far mostly
inaccessible and only deep grey matter can be
visualized.
• Ratings and measurements are subjective to a
certain extent, as size measurements of the SN
for instance are highly depending on the correct
plane chosen.
• Complete blinding of the investigator to the
participant’s age and disorder is not always
possible

48. Take home messages
• TCS investigations are representing an interesting
novel approach which should be considered in
the future by clinicians to improve diagnostics
and treatment decisions once the open questions
have been addressed.
• Multiple studies have demonstrated the validity
of BR hypoechogenicity of MD patients.
• SN hyperechogenicity could be a valuable marker
in paediatric ADHD patients.