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NEUROSONOLOGY
DR. PIYUSH OJHA
DM RESIDENT
DEPARTMENT OF NEUROLOGY
GOVT MEDICAL COLLEGE, KOTA
• Definition : Ultrasonic imaging of the brain and other neural
structures.
• Includes :
– Transcranial Doppler ultrasound
– Ultrasound of Nerves
– Carotid Ultrasound
TRANSCRANIAL DOPPLER
ULTRASOUND (TCD)
• TCD provides rapid, relatively inexpensive, noninvasive,
real-time measures of blood flow characteristics and
cerebrovascular hemodynamics within the basal arteries of
the brain.
• Can be used to measure flow velocity in the basal arteries of
the brain to assess relative changes in flow, diagnose focal
vascular stenosis, or to detect embolic signals within these
arteries.
• Can also be used to assess the physiologic health of a
particular vascular territory by :
– measuring blood flow responses to changes in blood
pressure (cerebral autoregulation)
– changes in end-tidal CO2 (cerebral vasoreactivity) or
– cognitive and motor activation (neurovascular coupling or
functional hyperemia).
• TCD is the most convenient way to monitor vascular changes
in response to interventions during acute cerebrovascular
events at the bedside.
• Established utility in the clinical diagnosis of a number of
cerebrovascular disorders such as acute ischemic stroke,
vasospasm, SAH, sickle cell disease, as well as other
conditions such as brain death.
• Physiologic data obtained from these measurements are
complementary to structural data obtained from various
modes of currently available vascular imaging.
• Clinical indication and research applications for this mode of
imaging continue to expand.
BASIC PRINCIPLES
• Principle - Doppler effect.
• Ultrasound waves emitted from the Doppler probe are
transmitted through the skull and reflected by moving RBCs
within the intracerebral vessels.
• The difference in the frequency between the emitted and
reflected waves (Doppler shift frequency) is directly
proportional to the speed of the moving RBCs (blood flow
velocity).
• Because blood flow within the vessel is laminar, the Doppler
signal obtained actually represents a mixture of different
Doppler frequency shifts forming a spectral display of the
distribution of the velocities of individual RBCs on the TCD
monitor.
• Spectral analysis can then be used to obtain measures of
blood flow velocity, as well as a few other characteristics of
flow within the insonated blood vessel.
• The specific parameters obtained from this spectral analysis
include Peak systolic velocity (Vs), End diastolic velocity (Vd),
Systolic upstroke or acceleration time, Pulsatility index (PI),
and time-averaged mean maximum velocity (Vmean ).
• The V mean is a continuous trace of peak velocities as a
function of time and in most TCD instruments, it is calculated
and displayed automatically.
• The propagation speed of a wave - a constant that can be
obtained for various mediums (speed in soft tissue is 1541 m/s).
•Theta (θ) = the angle of insonation.
•If angle = 0, i.e. the emitted wave is parallel to the direction of
flow - the most accurate measure of flow velocity.
•The larger the angle, the greater is the error in velocity measure.
•Therefore, it is important to minimize this angle to < 30 degrees
to keep the error below 15%.
Physiologic Determinants of Blood Flow
Velocity and Indices
• A number of physiologic variables can impact blood flow
velocity as measured by TCD.
• For eg. Age, gender, hematocrit, viscosity, carbon dioxide,
temperature, blood pressure, and mental or motor activity.
• Therefore, it is important to remember that during the course
of a TCD study, any measured differences in blood flow
velocity should be interpreted in the context of these
variables.
• All studies should be conducted with the patients at rest—not
speaking or moving their limbs.
• Blood flow velocities in the basal arteries of the brain decline
@ 0.3 to 0.5% per year between 20 to 70 years of age.
• Women have been shown to have higher flow velocities than
men between 20 to 60 years of age - difference may be
explained by the lower hematocrit in premenopausal women.
• no detectable gender difference - >70 years.
• Hematocrit and viscosity are inversely related to cerebral
blood flow velocity.
• Best exemplified in children with Sickle cell anemia who have
a significant drop in their mean flow velocities after a blood
transfusion.
• Blood flow velocities increase by 20% with a drop in
hematocrit from 40% to 30%.
• Partial pressure of CO2 - major influence on cerebral blood
flow velocity.
• Measured blood flow velocity can also be higher with higher
systemic BP despite an intact autoregulatory system.
• Particularly important in patients with SAH who are
monitored for cerebral vasospasm as manifested by elevated
cerebral blood flow velocity and who may simultaneously be
undergoing induced hypertension to treat vasospasm.
• The effect of temperature on cerebral blood flow velocities -
not well established.
TYPES OF TRANSCRANIAL DOPPLER DEVICES
• Two types of TCD equipment are currently available:
Nonduplex (nonimaging) and Duplex (imaging) devices.
• In Nonduplex devices, the arteries are identified “blindly”
based on the audible Doppler shift and the spectral display.
• Specific vessel identification is based on standard criteria,
which includes the cranial window used, orientation of the
probe, depth of sample volume, direction of blood flow,
relationship to the terminal internal carotid artery, and
response to various maneuvers such as the common carotid
artery compression.
• The imaging B-mode transcranial color-coded duplex (TCCD)
combines pulsed wave Doppler ultrasound with a cross-
sectional view of the area of insonation, which allows
identification of the arteries in relation to various anatomic
locations.
• The color-coded Doppler also depicts the direction of the flow
in relation to the probe (transducer) while recording blood
flow velocities.
• However, in TCCD, the angle of insonation can be measured
and used to correct the flow velocity measurement.
THE TRANSCRANIAL DOPPLER EXAMINATION
• Performed using a 2 MHz frequency ultrasound probe.
• The higher frequency probes used in extracranial Doppler
studies not applicable for intracranial measurements because
higher frequency waves are not able to adequately penetrate
through the skull.
• Insonation of the cerebral arteries only possible through
thinner regions of the skull, termed Acoustic windows.
• Therefore, familiarity with the anatomic location of cerebral
arteries relative to the acoustic windows and blood flow
velocities for the various arteries is critical for accurate blood
flow measurements through the nonduplex mode.
• In general, four main acoustic windows have been described:
– The Transtemporal window
– the Transorbital window
– the Suboccipital window
– the Submandibular window and
• Although each window has unique advantages for different
arteries and indications, a complete TCD examination should
include measurements from all four windows and the course
of blood flow at various depths within each major branch of
the circle of Willis should be assessed.
CLINICAL APPLICATIONS OF
TRANSCRANIAL DOPPLER ULTRASOUND
• SAH and cerebral vasospasm
• Intracranial steno-occlusive diseases
• Acute Ischemic stroke
• Collateral flow
• Sickle cell disease
• Microemboli detection
• Cerebral circulatory arrest
• RESEARCH APPLICATIONS AND FUTURE IMPLICATIONS :-
– Cerebral Autoregulation
– Cerebral vasoreactivity
– Neovascular coupling (Functional Hyperemia)
– Traumatic brain injury
– Intraoperative TCD monitoring
– TCD in dementia
CLINICAL APPLICATIONS OF TCD
1. SUBARACHNOID HEMORRHAGE & CEREBRAL VASOSPASM
• Angiographic cerebral vasospasm (VSP) occurs in 2/3 patients
with aneurysmal SAH with half becoming symptomatic.
• Significant direct correlation between VSP severity after SAH
and flow velocities in most cerebral arteries.
• TCD is much more sensitive for detecting proximal versus
distal VSP.
• Proximal VSP in any intracranial artery results in segmental or
diffuse elevations of the mean flow velocities without a
parallel flow velocity increase in the feeding extracranial
arteries such as the carotid or the vertebral arteries.
• The Lindegaard ratio (LR), defined as the ratio between the
time mean average (Vmean) velocity of the MCA to ICA helps
differentiate hyperemia from VSP.
• Hyperemia would result in flow elevations in both the MCA
and ICA and result in an LR < 3, whereas VSP would
preferentially elevate the MCA flow over the ICA with LR > 6.
• LR between 3 and 6 is a sign of mild VSP and > 6 is an
indication of severe VSP.
• Since distal VSP cannot be insonated - , increased Pulsatility
Index, indicating increased resistance distal to the site of
insonation, is used as a surrogate measure of distal VSP.
• In general, TCD flow velocity criteria - most reliable for
detecting angiographic MCA and basilar artery VSP.
• Some of the findings in MCA VSP include:
– MCA Vmean > 180 cm/s
– a sudden rise in MCA Vmean by > 65 cm/s or 20% increase
within a day during posthemorrhage days 3 to 7
– LR > 6 and
– abrupt increase in PI > 1.5 in two or more arteries
suggesting increase in ICP and/or VSP.
• TCD is most useful in monitoring the temporal course of
angiographic VSP following SAH.
• Sporadic measurements, especially if started after the
development of vasospasm, are less useful.
2. INTRACRANIAL STENO-OCCLUSIVE DISEASE
• Intracranial atherosclerosis is a significant risk factor for
ischemic strokes and transient ischemic attacks (TIAs),
accounting for 10% of such events.
• TCD can be used to detect stenosis and occlusion of the
carotid siphon, proximal MCA, ACA, PCA, and basilar as well as
intracranial vertebral arteries.
• Due to the greater tortuosity and anatomic variability of the
vessels in the posterior circulation, the sensitivity, specificity,
positive predictive value, and negative predictive value of TCD
is generally higher in the anterior circulation.
• Diagnosis of stenosis > 50% using TCD is based on the
following criteria:
(1) acceleration of flow velocity through the stenotic segment
(2) decrease in velocity distal to the stenotic segment
(poststenotic dilatation)
(3) side-to-side differences in mean flow velocity and
(4) disturbances in flow (i.e., turbulence and murmurs).
• Intracranial occlusion diagnosed by absence of flow at the
normal position and depth for a specific vessel (despite
adequate “acoustic window” and visualised other vessels in
the vicinity)
• In addition, one may also find that flow velocities are
increased in other intracranial vessels due to activation of
collateral vessels.
3. ACUTE ISCHEMIC STROKE
• TCD particularly useful in acute ischemic stroke where
repeated TCD studies can be used to track the course of an
arterial occlusion before and after thrombolysis.
• TCD can detect acute MCA occlusions with high (> 90%)
sensitivity,specificity, and positive and negative predictive
values.
• Can also detect occlusion in the ICA siphon, vertebral, and
basilar arteries with reasonable (70 to 90%) sensitivity and
positive predictive value and excellent specificity and negative
predictive value (> 90%).
• Recent studies suggest that ultrasound may also have an
independent effect in augmenting thrombolysis of the
occluded vessel in patients presenting with acute thrombosis.
(Eggers J et al : Effect of ultrasound on thrombolysis of
middle cerebral artery occlusion. Ann Neurol
2003;53(6):797–800)
• Continuous TCD recording significantly increased tPA-induced
arterial recanalization in the Clotbust trial.
• In this trial, 83% of patients achieved either partial or
complete recanalization with tPA and TCD monitoring
compared with 50% recanalization with tPA treatment alone.
• Early TCD findings can be very useful for prognosis in patients
presenting with acute ischemic stroke.
• Intracranial arterial occlusion detected by TCD is associated
with poor 90-day outcome, whereas a normal TCD study is
predictive of early recovery.
• Delayed (> 6 h) spontaneous recanalization as demonstrated
by TCD, is also independently associated with greater risk of
hemorrhagic transformation.
• In a recent study of 489 patients with recent TIA or minor
stroke, mean flow velocity and the ratio of pulsatility to mean
flow velocity were independent risk factors for not only stroke
recurrence, but also the occurrence of other major vascular
events (stroke, myocardial infarction, and vascular death)
4. COLLATERAL FLOW
• Knowledge of collateral flow patterns of the basal arteries of
the brain has significant clinical implications in the
management of patients with cerebrovascular
atherothrombotic disease.
• Degree of collateral flow is correlated with infarct volume and
clinical outcome in patients with ischemic stroke.
• TCD can provide real-time information regarding the direction
and the velocity of blood flow in known intracranial collateral
channels, which become active in acute and/or chronic steno-
occlusive cerebrovascular diseases.
5. SICKLE CELL DISEASE
• Children with sickle cell disease (SCD) have chronic hemolysis
resulting in low hemoglobin levels.
• Chronic anemia and hypoxia trigger angiogenesis and
neovascularization.
• In addition, the interaction of the sickled red cells with the
endothelium causes inflammation and intracranial stenosis.
• The compromised vascular system predisposes these children
to both ischemic and hemorrhagic infarcts.
• An increase Vmean > 200 cm/s in the ICA or MCA detected by
TCD has been shown to be associated with increased risk of
ischemic stroke in these children.
• In the Stroke Prevention Trial in Sickle Cell Disease (STOP),
children between 2 to 16 years old with no history of stroke
and MCA velocity threshold of 200 cm/s were randomly
allocated to standard care or to periodic blood transfusion
therapy to lower the hemoglobin S concentration to < 30% of
total hemoglobin.
• Blood transfusion based on mean flow velocity resulted in
92% stroke risk reduction.
• Following the TCD criteria in the STOP trial, a fivefold decrease
in the rate of first stroke was observed in children with SCD.
• In a retrospective cohort of 475 children, the incidence of
stroke declined 10-fold following TCD screening and
prophylactic blood transfusion over an 8-year period.
• The STOP II trial assessed the safety of discontinuing long-
term blood transfusion in children who had normal MCA flow
velocities and who had received transfusions for 30 months or
longer.
• The study was stopped early due to increased MCA flow
velocities and new ischemic strokes in the group that
discontinued transfusion.
• There were no strokes in the group that continued periodic
transfusion.
• Because early TCD screening coupled with prophylactic
transfusion seems to reduce overt stroke in children with SCD,
TCD assessment should now be a routine component of
preventive care for these children.
• TCD screening should be avoided during acute illnesses
because factors such as hypoxia, fever, hypoglycemia, and
worsening anemia may impact flow velocity measures.
• The impact of TCD based transfusion on subsequent stroke
risk has not been studied in adults with SCD.
6. MICRO-EMBOLI DETECTION
• TCD is the only medical device that can detect circulating
cerebral microemboli, both solid and gaseous, in real-time.
• Based on backscatter of the ultrasound waves from the
emboli resulting in high-intensity transient signals (HITS) or
embolic signals in the Doppler spectrum as they travel
through the insonated vessel.
• The backscatter of the ultrasound from gaseous emboli are
higher than that of solid emboli of a similar size, which in turn
is higher than the backscatter observed from red blood cells
within normal flow.
• Embolic signals using TCD ultrasound - detected in patients
with carotid stenosis, myocardial infarction, atrial fibrillation,
and mechanical cardiac valves.
• The role of TCD in antithrombotic therapy was subsequently
investigated in the CARESS (Clopidogrel and Aspirin for
Reduction of Emboli in Symptomatic Carotid Stenosis) trial,
which tested the effect of antithrombotic medications on
patients with symptomatic carotid stenosis > 50%.
• Patients with embolic signals were randomized to
combination antithrombotic therapy with clopidogrel and
aspirin or to aspirin therapy alone.
• TCD recording in the ipsilateral MCA on day 7 of the treatment
showed that the combination therapy was more effective
than aspirin alone in reducing embolic signals.
7. CEREBRAL CIRCULATORY ARREST
• A decrease in cerebral perfusion pressure associated with
increases in ICP and PI result in compression of the
intracranial arteries and cessation of flow to the brain, leading
to cerebral circulatory arrest (CCA).
• The pattern of cerebral blood flow leading to CCA and brain
death can be visualized by TCD and monitored continuously at
bedside.
• When the ICP increases to match the diastolic perfusion
pressure, diastolic cerebral blood flow approaches zero.
• With continued rise in ICP, diastolic blood flow reappears, but
it is in the opposite direction (reversed flow), visualized as
retrograde flow in the TCD.
• Systolic waveforms also become spiked.
• The retrograde or oscillatory diastolic flow along with systolic
spikes, result in no net forward cerebral blood flow and are
characteristic of CCA.
• TCD has very high sensitivity (96.5%) and specificity (100%) in
the diagnosis of cerebral circulatory arrest, but the possibility
of temporary arrest should be excluded by having the systolic
blood pressure > 70 mm Hg during the TCD assessment.
Role of Ultrasound in evaluation of
Peripheral Nerves
• In 1988, Fornage produced the first review of imaging findings
of peripheral nerves using sonography.
• USG remains an underutilized modality
• An excellent cost-effective modality in imaging of peripheral
nerves.
• The newer high-frequency probes allow high-resolution
imaging at relatively superficial location.
• USG can detect and evaluate traumatic, inflammatory,
infective, neoplastic, and compressive pathologies of the
peripheral nerves.
TECHNIQUE
• Almost all the nerves including digital nerves can be imaged
by USG.
• Before starting the scan of a peripheral nerve in a particular
region, one needs to know the detailed anatomy.
• A high-frequency linear array probe (8-15 MHz) is used.
• The examination is started from a known anatomic landmark
near the nerve.
• Once the nerve is localized in the short axis, it is traced
cranially and caudally to see for contour and architectural
abnormality.
• If pathology is encountered, then the attention is focused on
that particular segment.
• The probe is then turned in the long axis of the nerve and the
pathology is evaluated.
• Movement of limb helps to differentiate nerve from tendons,
whereas Color Doppler helps to differentiate nerves from
vessels.
• Lymph nodes are spherical and show a fatty hilum and can be
easily differentiated from nerves by their shape and inability
to trace them in longitudinal axis.
• The Normal nerve :
– Transverse section - reveals small hypoechoic areas
separated by hyperechoic septae, giving a “honeycomb-
like” appearance. The hypoechoic areas represent nerve
fascicles while the echogenic septae represent
interfascicular perineurium.
– Longitudinal sections - also reveal the fascicular
architecture, leading to a “bundle of straws” appearance.
– Normaly nerves have no detectable doppler flow (unless
injured or streched).
• Nerve is more echogenic compared to the muscle which
shows hypoechoic muscle fiber bundles with intervening
echogenic perimysium.
• The tendon more echogenic as compared to the nerve and
shows a compact arrangement of echogenic fibrils.
• Zaidman et al. (NEUROLOGY 2013) :
– Retrospectively compared accuracy of ultrasound and MRI
for detecting focal peripheral nerve pathology, excluding
idiopathic Carpal or Cubital tunnel syndromes.
– Ultrasound is more sensitive than MRI (93% vs 67%), has
equivalent specificity (86%), and better identifies
multifocal lesions than MRI.
– In sonographically accessible regions ultrasound is the
preferred initial imaging modality for anatomic evaluation
of suspected peripheral nervous system lesions.
Axial USG image of normal nerve showing rounded hypoechoic areas separated by
hyperechoic septae, giving a “Honeycomb” appearance
Longitudinal USG image of normal nerve depicting hypoechoic linear fascicles with
intervening echogenic interfascicular perineurium i.e. “Bundle of straws” appearance
ULTRASOUND APPEARANCE OF
VARIOUS PATHOLOGIES
1. TRAUMA
• Nerve injuries are broadly classified as : Neurapraxia,
Axonotmesis, and Neurotmesis.
• Neurapraxia is injury with maintenance of nerve continuity.
• Axonotmesis is disruption of axons and myelin with intact
epi-and perineurium
• Neurotmesis is complete disruption of the nerve.
• Neurapraxia and axonotmesis have good chances of
recovery, while neurotmesis does not usually recover
without surgery
• USG can be used to detect and demonstrate :-
– the site of injury
– differentiate nerve injury in continuity from nerve
transaction
– evaluate the cause of compression, and
– detect foreign bodies as well as neuroma or scarring.
• USG also useful in localizing iatrogenic nerve injury following
limb lengthening procedures or due to orthopedic implants
where magnetic resonance imaging (MRI) may be limited
due to susceptibility artifacts.
• High resolution USG allows evaluation of small nerves like
digital nerves which may be difficult with MRI.
• Also, MRI may not differentiate neural contusion from nerve
disruption.
• Electrodiagnostic studies do not demonstrate morphologic
information like site and degree of injury. Hence, USG has an
important role to play in evaluation of patients with suspected
nerve injury.
• Neurapraxic injury is seen as swollen nerve with hypoechoic
appearance.
• Complete and partial transection of nerves can be
differentiated by USG.
• In cases with transection, it is important to provide the
distance between the stumps as it helps in deciding surgical
management.
• Stump or amputation neuromas (reactive thickening of the
nerves and not true tumors) may be seen as focal thickening
or mass-like lesions at the nerve ends .
(A) Longitudinal and (B) axial USG images in a patient with previous history of fracture
repair of humerus at the elbow. The K wire is impinging on the nerve, causing chronic
nerve degeneration seen as hypoechoic appearance of nerve with loss of normal
fascicular architecture
Longitudinal USG image reveals complete transection of the volar digital nerve of
middle finger following penetrating injury
Longitudinal USG image shows complete transection of the radial nerve following old
penetrating trauma.
Note the Amputation neuromas at both the cut ends seen as bulbous lesions
2. TUMORS
• Most common nerve tumors are nerve sheath tumors which
include Schwannomas and Neurofibromas.
• It may not always be possible to differentiate between them
on USG.
• Seen as well-defined ovoid homogeneous hypoechoic lesions
with nerve entering and exiting from them.
• Schwannomas are eccentric along the long axis of nerve, with
nerve fascicles seen separately.
• Neurofibromas are spindle-shaped with loss of normal
fascicular architecture
(A) Longitudinal USG image showing a fusiform predominantly hypoechoic mass lesion
along the median nerve in forearm. The nerve can be located eccentrically along the
ventral aspect of the mass lesion, suggesting the diagnosis of Schwannoma
(B) Intraoperative image of the lesion confirming the ultrasound findings
(C) Intraoperative image after excision of the mass lesion with preservation of the nerve
3. INFECTIVE LESIONS
• In India, leprosy is a common treatable condition whose
hallmark is nerve enlargement and inflammation.
• Clinical examination may be subjective and inaccurate.
• Also, many nerves may not be amenable to palpation.
• Early detection of nerve impairment can help in preventing
disability.
• USG can provide objective evidence of nerve enlargement and
also evaluate its internal architecture.
• In leprosy, the nerves may show enlargement as well as
edema, loss of fascicular architecture, and increased peri- and
endoneurium vascularity on Doppler.
• Jain et al. have demonstrated these changes in ulnar, median,
lateral peroneal, and popliteal nerves.
(A) Longitudinal USG image and (B) Color Doppler image of median nerve in a patient
with leprosy. The entire nerve is thickened with loss of fascicular architecture and
hypoechoic appearance. There is increased endoneurium and perineurium vascularity
on color Doppler
4. ENTRAPMENT NEUROPATHIES
• Often unrecognized cause of pain and neural impairment.
• The nerves are more prone to compression in specific
locations where they course through osteofibrous tunnels.
• The median nerve in carpal tunnel and the ulnar nerve in
Guyon's canal and cubital tunnel are the common sites of
entrapment in the upper limb and can be evaluated with USG.
• Common peroneal nerve near fibular neck and posterior tibial
nerve in tarsal tunnel are commonly involved in the lower
limb.
• Carpal tunnel syndrome - most common entrapment
neuropathy.
• Occurs due to compression of the median nerve in the carpal
tunnel bounded by the carpal bones and the flexor
retinaculum.
• The diagnosis is based on the patient's history of sensory and
motor symptoms in median nerve distribution and clinical
examination findings.
• USG is comparable with nerve conduction studies in the
diagnosis of carpal tunnel syndrome.
• It shows the classic triad of (Buchberger et al) :-
– enlargement of the nerve at the level of distal radius and
proximal carpal tunnel
– flattening of the nerve in distal carpal tunnel and
– palmar bowing of the flexor retinaculum.
• A cross-sectional area of the median nerve proximal to the
tunnel inlet more than 10 mm2 is abnormal.
• The abrupt change in nerve caliber at the entrance of carpal
tunnel is called “notch sign”.
• The nerve may show a homogeneous hypoechoic appearance
with loss of fascicular echopattern
• A contralateral comparison usually helps in detecting subtle
signs to reach the diagnosis.
Longitudinal USG image of Normal median nerve proximal to and in the carpal tunnel.
T: Flexor tendons in the carpal tunnel; MN: Median nerve
(A) Longitudinal USG image shows enlargement of the median nerve at carpal tunnel
inlet and outlet in carpal tunnel syndrome.
(B) Axial USG image shows increase in cross-sectional area of the median nerve proximal
to the tunnel. It is 12.6 mm2 .Normal being less than 10 mm2
(A) Longitudinal USG image reveals abrupt change in the caliber of median nerve at
the entrance of carpal tunnel (Notch sign) in carpal tunnel syndrome.
(B) Intraoperative image confirming the ultrasound findings
THANK YOU
REFERENCES
• Transcranial Doppler Ultrasound: Technique and Application :
Sushmita Purkayastha, Farzaneh Sorond : Seminars in
Neurology 2012;32:411–420.
• Textbook of Emergency Neuroradiology : T Scarabino
• Role of ultrasound in evaluation of peripheral nerves : Ashwin
D et al : Indian J Radiol Imaging. 2014 Jul-Sep; 24(3): 254–258.
• High-Resolution Sonography of Lower Extremity Peripheral
Nerves: Anatomic Correlation and Spectrum of Disease :
Siegfried Peer et al : J Ultrasound Med 21:315–322, 2002
• Sonography of Peripheral Nerve Pathology : R. M. Stuart et al :
American Journal of Roentgenology. 2004;182: 123-129.
• Bradley’s Neurology in clinical Practice : 7th edition

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Neurosonology

  • 1. NEUROSONOLOGY DR. PIYUSH OJHA DM RESIDENT DEPARTMENT OF NEUROLOGY GOVT MEDICAL COLLEGE, KOTA
  • 2. • Definition : Ultrasonic imaging of the brain and other neural structures. • Includes : – Transcranial Doppler ultrasound – Ultrasound of Nerves – Carotid Ultrasound
  • 4. • TCD provides rapid, relatively inexpensive, noninvasive, real-time measures of blood flow characteristics and cerebrovascular hemodynamics within the basal arteries of the brain. • Can be used to measure flow velocity in the basal arteries of the brain to assess relative changes in flow, diagnose focal vascular stenosis, or to detect embolic signals within these arteries.
  • 5. • Can also be used to assess the physiologic health of a particular vascular territory by : – measuring blood flow responses to changes in blood pressure (cerebral autoregulation) – changes in end-tidal CO2 (cerebral vasoreactivity) or – cognitive and motor activation (neurovascular coupling or functional hyperemia). • TCD is the most convenient way to monitor vascular changes in response to interventions during acute cerebrovascular events at the bedside.
  • 6. • Established utility in the clinical diagnosis of a number of cerebrovascular disorders such as acute ischemic stroke, vasospasm, SAH, sickle cell disease, as well as other conditions such as brain death. • Physiologic data obtained from these measurements are complementary to structural data obtained from various modes of currently available vascular imaging. • Clinical indication and research applications for this mode of imaging continue to expand.
  • 7. BASIC PRINCIPLES • Principle - Doppler effect. • Ultrasound waves emitted from the Doppler probe are transmitted through the skull and reflected by moving RBCs within the intracerebral vessels. • The difference in the frequency between the emitted and reflected waves (Doppler shift frequency) is directly proportional to the speed of the moving RBCs (blood flow velocity). • Because blood flow within the vessel is laminar, the Doppler signal obtained actually represents a mixture of different Doppler frequency shifts forming a spectral display of the distribution of the velocities of individual RBCs on the TCD monitor.
  • 8. • Spectral analysis can then be used to obtain measures of blood flow velocity, as well as a few other characteristics of flow within the insonated blood vessel. • The specific parameters obtained from this spectral analysis include Peak systolic velocity (Vs), End diastolic velocity (Vd), Systolic upstroke or acceleration time, Pulsatility index (PI), and time-averaged mean maximum velocity (Vmean ). • The V mean is a continuous trace of peak velocities as a function of time and in most TCD instruments, it is calculated and displayed automatically.
  • 9.
  • 10. • The propagation speed of a wave - a constant that can be obtained for various mediums (speed in soft tissue is 1541 m/s). •Theta (θ) = the angle of insonation. •If angle = 0, i.e. the emitted wave is parallel to the direction of flow - the most accurate measure of flow velocity. •The larger the angle, the greater is the error in velocity measure. •Therefore, it is important to minimize this angle to < 30 degrees to keep the error below 15%.
  • 11. Physiologic Determinants of Blood Flow Velocity and Indices • A number of physiologic variables can impact blood flow velocity as measured by TCD. • For eg. Age, gender, hematocrit, viscosity, carbon dioxide, temperature, blood pressure, and mental or motor activity. • Therefore, it is important to remember that during the course of a TCD study, any measured differences in blood flow velocity should be interpreted in the context of these variables. • All studies should be conducted with the patients at rest—not speaking or moving their limbs.
  • 12. • Blood flow velocities in the basal arteries of the brain decline @ 0.3 to 0.5% per year between 20 to 70 years of age. • Women have been shown to have higher flow velocities than men between 20 to 60 years of age - difference may be explained by the lower hematocrit in premenopausal women. • no detectable gender difference - >70 years. • Hematocrit and viscosity are inversely related to cerebral blood flow velocity. • Best exemplified in children with Sickle cell anemia who have a significant drop in their mean flow velocities after a blood transfusion. • Blood flow velocities increase by 20% with a drop in hematocrit from 40% to 30%.
  • 13. • Partial pressure of CO2 - major influence on cerebral blood flow velocity. • Measured blood flow velocity can also be higher with higher systemic BP despite an intact autoregulatory system. • Particularly important in patients with SAH who are monitored for cerebral vasospasm as manifested by elevated cerebral blood flow velocity and who may simultaneously be undergoing induced hypertension to treat vasospasm. • The effect of temperature on cerebral blood flow velocities - not well established.
  • 14. TYPES OF TRANSCRANIAL DOPPLER DEVICES • Two types of TCD equipment are currently available: Nonduplex (nonimaging) and Duplex (imaging) devices. • In Nonduplex devices, the arteries are identified “blindly” based on the audible Doppler shift and the spectral display. • Specific vessel identification is based on standard criteria, which includes the cranial window used, orientation of the probe, depth of sample volume, direction of blood flow, relationship to the terminal internal carotid artery, and response to various maneuvers such as the common carotid artery compression.
  • 15. • The imaging B-mode transcranial color-coded duplex (TCCD) combines pulsed wave Doppler ultrasound with a cross- sectional view of the area of insonation, which allows identification of the arteries in relation to various anatomic locations. • The color-coded Doppler also depicts the direction of the flow in relation to the probe (transducer) while recording blood flow velocities. • However, in TCCD, the angle of insonation can be measured and used to correct the flow velocity measurement.
  • 16. THE TRANSCRANIAL DOPPLER EXAMINATION • Performed using a 2 MHz frequency ultrasound probe. • The higher frequency probes used in extracranial Doppler studies not applicable for intracranial measurements because higher frequency waves are not able to adequately penetrate through the skull. • Insonation of the cerebral arteries only possible through thinner regions of the skull, termed Acoustic windows. • Therefore, familiarity with the anatomic location of cerebral arteries relative to the acoustic windows and blood flow velocities for the various arteries is critical for accurate blood flow measurements through the nonduplex mode.
  • 17. • In general, four main acoustic windows have been described: – The Transtemporal window – the Transorbital window – the Suboccipital window – the Submandibular window and • Although each window has unique advantages for different arteries and indications, a complete TCD examination should include measurements from all four windows and the course of blood flow at various depths within each major branch of the circle of Willis should be assessed.
  • 18.
  • 19.
  • 20. CLINICAL APPLICATIONS OF TRANSCRANIAL DOPPLER ULTRASOUND • SAH and cerebral vasospasm • Intracranial steno-occlusive diseases • Acute Ischemic stroke • Collateral flow • Sickle cell disease • Microemboli detection • Cerebral circulatory arrest
  • 21. • RESEARCH APPLICATIONS AND FUTURE IMPLICATIONS :- – Cerebral Autoregulation – Cerebral vasoreactivity – Neovascular coupling (Functional Hyperemia) – Traumatic brain injury – Intraoperative TCD monitoring – TCD in dementia
  • 22. CLINICAL APPLICATIONS OF TCD 1. SUBARACHNOID HEMORRHAGE & CEREBRAL VASOSPASM • Angiographic cerebral vasospasm (VSP) occurs in 2/3 patients with aneurysmal SAH with half becoming symptomatic. • Significant direct correlation between VSP severity after SAH and flow velocities in most cerebral arteries. • TCD is much more sensitive for detecting proximal versus distal VSP. • Proximal VSP in any intracranial artery results in segmental or diffuse elevations of the mean flow velocities without a parallel flow velocity increase in the feeding extracranial arteries such as the carotid or the vertebral arteries.
  • 23. • The Lindegaard ratio (LR), defined as the ratio between the time mean average (Vmean) velocity of the MCA to ICA helps differentiate hyperemia from VSP. • Hyperemia would result in flow elevations in both the MCA and ICA and result in an LR < 3, whereas VSP would preferentially elevate the MCA flow over the ICA with LR > 6. • LR between 3 and 6 is a sign of mild VSP and > 6 is an indication of severe VSP. • Since distal VSP cannot be insonated - , increased Pulsatility Index, indicating increased resistance distal to the site of insonation, is used as a surrogate measure of distal VSP.
  • 24. • In general, TCD flow velocity criteria - most reliable for detecting angiographic MCA and basilar artery VSP. • Some of the findings in MCA VSP include: – MCA Vmean > 180 cm/s – a sudden rise in MCA Vmean by > 65 cm/s or 20% increase within a day during posthemorrhage days 3 to 7 – LR > 6 and – abrupt increase in PI > 1.5 in two or more arteries suggesting increase in ICP and/or VSP. • TCD is most useful in monitoring the temporal course of angiographic VSP following SAH. • Sporadic measurements, especially if started after the development of vasospasm, are less useful.
  • 25. 2. INTRACRANIAL STENO-OCCLUSIVE DISEASE • Intracranial atherosclerosis is a significant risk factor for ischemic strokes and transient ischemic attacks (TIAs), accounting for 10% of such events. • TCD can be used to detect stenosis and occlusion of the carotid siphon, proximal MCA, ACA, PCA, and basilar as well as intracranial vertebral arteries. • Due to the greater tortuosity and anatomic variability of the vessels in the posterior circulation, the sensitivity, specificity, positive predictive value, and negative predictive value of TCD is generally higher in the anterior circulation.
  • 26. • Diagnosis of stenosis > 50% using TCD is based on the following criteria: (1) acceleration of flow velocity through the stenotic segment (2) decrease in velocity distal to the stenotic segment (poststenotic dilatation) (3) side-to-side differences in mean flow velocity and (4) disturbances in flow (i.e., turbulence and murmurs). • Intracranial occlusion diagnosed by absence of flow at the normal position and depth for a specific vessel (despite adequate “acoustic window” and visualised other vessels in the vicinity) • In addition, one may also find that flow velocities are increased in other intracranial vessels due to activation of collateral vessels.
  • 27. 3. ACUTE ISCHEMIC STROKE • TCD particularly useful in acute ischemic stroke where repeated TCD studies can be used to track the course of an arterial occlusion before and after thrombolysis. • TCD can detect acute MCA occlusions with high (> 90%) sensitivity,specificity, and positive and negative predictive values. • Can also detect occlusion in the ICA siphon, vertebral, and basilar arteries with reasonable (70 to 90%) sensitivity and positive predictive value and excellent specificity and negative predictive value (> 90%).
  • 28. • Recent studies suggest that ultrasound may also have an independent effect in augmenting thrombolysis of the occluded vessel in patients presenting with acute thrombosis. (Eggers J et al : Effect of ultrasound on thrombolysis of middle cerebral artery occlusion. Ann Neurol 2003;53(6):797–800) • Continuous TCD recording significantly increased tPA-induced arterial recanalization in the Clotbust trial. • In this trial, 83% of patients achieved either partial or complete recanalization with tPA and TCD monitoring compared with 50% recanalization with tPA treatment alone.
  • 29. • Early TCD findings can be very useful for prognosis in patients presenting with acute ischemic stroke. • Intracranial arterial occlusion detected by TCD is associated with poor 90-day outcome, whereas a normal TCD study is predictive of early recovery. • Delayed (> 6 h) spontaneous recanalization as demonstrated by TCD, is also independently associated with greater risk of hemorrhagic transformation. • In a recent study of 489 patients with recent TIA or minor stroke, mean flow velocity and the ratio of pulsatility to mean flow velocity were independent risk factors for not only stroke recurrence, but also the occurrence of other major vascular events (stroke, myocardial infarction, and vascular death)
  • 30. 4. COLLATERAL FLOW • Knowledge of collateral flow patterns of the basal arteries of the brain has significant clinical implications in the management of patients with cerebrovascular atherothrombotic disease. • Degree of collateral flow is correlated with infarct volume and clinical outcome in patients with ischemic stroke. • TCD can provide real-time information regarding the direction and the velocity of blood flow in known intracranial collateral channels, which become active in acute and/or chronic steno- occlusive cerebrovascular diseases.
  • 31. 5. SICKLE CELL DISEASE • Children with sickle cell disease (SCD) have chronic hemolysis resulting in low hemoglobin levels. • Chronic anemia and hypoxia trigger angiogenesis and neovascularization. • In addition, the interaction of the sickled red cells with the endothelium causes inflammation and intracranial stenosis.
  • 32. • The compromised vascular system predisposes these children to both ischemic and hemorrhagic infarcts. • An increase Vmean > 200 cm/s in the ICA or MCA detected by TCD has been shown to be associated with increased risk of ischemic stroke in these children. • In the Stroke Prevention Trial in Sickle Cell Disease (STOP), children between 2 to 16 years old with no history of stroke and MCA velocity threshold of 200 cm/s were randomly allocated to standard care or to periodic blood transfusion therapy to lower the hemoglobin S concentration to < 30% of total hemoglobin. • Blood transfusion based on mean flow velocity resulted in 92% stroke risk reduction.
  • 33. • Following the TCD criteria in the STOP trial, a fivefold decrease in the rate of first stroke was observed in children with SCD. • In a retrospective cohort of 475 children, the incidence of stroke declined 10-fold following TCD screening and prophylactic blood transfusion over an 8-year period.
  • 34. • The STOP II trial assessed the safety of discontinuing long- term blood transfusion in children who had normal MCA flow velocities and who had received transfusions for 30 months or longer. • The study was stopped early due to increased MCA flow velocities and new ischemic strokes in the group that discontinued transfusion. • There were no strokes in the group that continued periodic transfusion.
  • 35. • Because early TCD screening coupled with prophylactic transfusion seems to reduce overt stroke in children with SCD, TCD assessment should now be a routine component of preventive care for these children. • TCD screening should be avoided during acute illnesses because factors such as hypoxia, fever, hypoglycemia, and worsening anemia may impact flow velocity measures. • The impact of TCD based transfusion on subsequent stroke risk has not been studied in adults with SCD.
  • 36. 6. MICRO-EMBOLI DETECTION • TCD is the only medical device that can detect circulating cerebral microemboli, both solid and gaseous, in real-time. • Based on backscatter of the ultrasound waves from the emboli resulting in high-intensity transient signals (HITS) or embolic signals in the Doppler spectrum as they travel through the insonated vessel. • The backscatter of the ultrasound from gaseous emboli are higher than that of solid emboli of a similar size, which in turn is higher than the backscatter observed from red blood cells within normal flow. • Embolic signals using TCD ultrasound - detected in patients with carotid stenosis, myocardial infarction, atrial fibrillation, and mechanical cardiac valves.
  • 37.
  • 38. • The role of TCD in antithrombotic therapy was subsequently investigated in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis) trial, which tested the effect of antithrombotic medications on patients with symptomatic carotid stenosis > 50%. • Patients with embolic signals were randomized to combination antithrombotic therapy with clopidogrel and aspirin or to aspirin therapy alone. • TCD recording in the ipsilateral MCA on day 7 of the treatment showed that the combination therapy was more effective than aspirin alone in reducing embolic signals.
  • 39. 7. CEREBRAL CIRCULATORY ARREST • A decrease in cerebral perfusion pressure associated with increases in ICP and PI result in compression of the intracranial arteries and cessation of flow to the brain, leading to cerebral circulatory arrest (CCA). • The pattern of cerebral blood flow leading to CCA and brain death can be visualized by TCD and monitored continuously at bedside. • When the ICP increases to match the diastolic perfusion pressure, diastolic cerebral blood flow approaches zero.
  • 40.
  • 41. • With continued rise in ICP, diastolic blood flow reappears, but it is in the opposite direction (reversed flow), visualized as retrograde flow in the TCD. • Systolic waveforms also become spiked. • The retrograde or oscillatory diastolic flow along with systolic spikes, result in no net forward cerebral blood flow and are characteristic of CCA. • TCD has very high sensitivity (96.5%) and specificity (100%) in the diagnosis of cerebral circulatory arrest, but the possibility of temporary arrest should be excluded by having the systolic blood pressure > 70 mm Hg during the TCD assessment.
  • 42. Role of Ultrasound in evaluation of Peripheral Nerves
  • 43. • In 1988, Fornage produced the first review of imaging findings of peripheral nerves using sonography. • USG remains an underutilized modality • An excellent cost-effective modality in imaging of peripheral nerves. • The newer high-frequency probes allow high-resolution imaging at relatively superficial location. • USG can detect and evaluate traumatic, inflammatory, infective, neoplastic, and compressive pathologies of the peripheral nerves.
  • 44. TECHNIQUE • Almost all the nerves including digital nerves can be imaged by USG. • Before starting the scan of a peripheral nerve in a particular region, one needs to know the detailed anatomy. • A high-frequency linear array probe (8-15 MHz) is used. • The examination is started from a known anatomic landmark near the nerve. • Once the nerve is localized in the short axis, it is traced cranially and caudally to see for contour and architectural abnormality.
  • 45. • If pathology is encountered, then the attention is focused on that particular segment. • The probe is then turned in the long axis of the nerve and the pathology is evaluated. • Movement of limb helps to differentiate nerve from tendons, whereas Color Doppler helps to differentiate nerves from vessels. • Lymph nodes are spherical and show a fatty hilum and can be easily differentiated from nerves by their shape and inability to trace them in longitudinal axis.
  • 46. • The Normal nerve : – Transverse section - reveals small hypoechoic areas separated by hyperechoic septae, giving a “honeycomb- like” appearance. The hypoechoic areas represent nerve fascicles while the echogenic septae represent interfascicular perineurium. – Longitudinal sections - also reveal the fascicular architecture, leading to a “bundle of straws” appearance. – Normaly nerves have no detectable doppler flow (unless injured or streched).
  • 47. • Nerve is more echogenic compared to the muscle which shows hypoechoic muscle fiber bundles with intervening echogenic perimysium. • The tendon more echogenic as compared to the nerve and shows a compact arrangement of echogenic fibrils.
  • 48. • Zaidman et al. (NEUROLOGY 2013) : – Retrospectively compared accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic Carpal or Cubital tunnel syndromes. – Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. – In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions.
  • 49. Axial USG image of normal nerve showing rounded hypoechoic areas separated by hyperechoic septae, giving a “Honeycomb” appearance
  • 50. Longitudinal USG image of normal nerve depicting hypoechoic linear fascicles with intervening echogenic interfascicular perineurium i.e. “Bundle of straws” appearance
  • 52. 1. TRAUMA • Nerve injuries are broadly classified as : Neurapraxia, Axonotmesis, and Neurotmesis. • Neurapraxia is injury with maintenance of nerve continuity. • Axonotmesis is disruption of axons and myelin with intact epi-and perineurium • Neurotmesis is complete disruption of the nerve. • Neurapraxia and axonotmesis have good chances of recovery, while neurotmesis does not usually recover without surgery
  • 53. • USG can be used to detect and demonstrate :- – the site of injury – differentiate nerve injury in continuity from nerve transaction – evaluate the cause of compression, and – detect foreign bodies as well as neuroma or scarring. • USG also useful in localizing iatrogenic nerve injury following limb lengthening procedures or due to orthopedic implants where magnetic resonance imaging (MRI) may be limited due to susceptibility artifacts.
  • 54. • High resolution USG allows evaluation of small nerves like digital nerves which may be difficult with MRI. • Also, MRI may not differentiate neural contusion from nerve disruption. • Electrodiagnostic studies do not demonstrate morphologic information like site and degree of injury. Hence, USG has an important role to play in evaluation of patients with suspected nerve injury.
  • 55. • Neurapraxic injury is seen as swollen nerve with hypoechoic appearance. • Complete and partial transection of nerves can be differentiated by USG. • In cases with transection, it is important to provide the distance between the stumps as it helps in deciding surgical management. • Stump or amputation neuromas (reactive thickening of the nerves and not true tumors) may be seen as focal thickening or mass-like lesions at the nerve ends .
  • 56. (A) Longitudinal and (B) axial USG images in a patient with previous history of fracture repair of humerus at the elbow. The K wire is impinging on the nerve, causing chronic nerve degeneration seen as hypoechoic appearance of nerve with loss of normal fascicular architecture
  • 57. Longitudinal USG image reveals complete transection of the volar digital nerve of middle finger following penetrating injury
  • 58. Longitudinal USG image shows complete transection of the radial nerve following old penetrating trauma. Note the Amputation neuromas at both the cut ends seen as bulbous lesions
  • 59. 2. TUMORS • Most common nerve tumors are nerve sheath tumors which include Schwannomas and Neurofibromas. • It may not always be possible to differentiate between them on USG. • Seen as well-defined ovoid homogeneous hypoechoic lesions with nerve entering and exiting from them. • Schwannomas are eccentric along the long axis of nerve, with nerve fascicles seen separately. • Neurofibromas are spindle-shaped with loss of normal fascicular architecture
  • 60. (A) Longitudinal USG image showing a fusiform predominantly hypoechoic mass lesion along the median nerve in forearm. The nerve can be located eccentrically along the ventral aspect of the mass lesion, suggesting the diagnosis of Schwannoma (B) Intraoperative image of the lesion confirming the ultrasound findings (C) Intraoperative image after excision of the mass lesion with preservation of the nerve
  • 61. 3. INFECTIVE LESIONS • In India, leprosy is a common treatable condition whose hallmark is nerve enlargement and inflammation. • Clinical examination may be subjective and inaccurate. • Also, many nerves may not be amenable to palpation. • Early detection of nerve impairment can help in preventing disability. • USG can provide objective evidence of nerve enlargement and also evaluate its internal architecture. • In leprosy, the nerves may show enlargement as well as edema, loss of fascicular architecture, and increased peri- and endoneurium vascularity on Doppler. • Jain et al. have demonstrated these changes in ulnar, median, lateral peroneal, and popliteal nerves.
  • 62. (A) Longitudinal USG image and (B) Color Doppler image of median nerve in a patient with leprosy. The entire nerve is thickened with loss of fascicular architecture and hypoechoic appearance. There is increased endoneurium and perineurium vascularity on color Doppler
  • 63. 4. ENTRAPMENT NEUROPATHIES • Often unrecognized cause of pain and neural impairment. • The nerves are more prone to compression in specific locations where they course through osteofibrous tunnels. • The median nerve in carpal tunnel and the ulnar nerve in Guyon's canal and cubital tunnel are the common sites of entrapment in the upper limb and can be evaluated with USG. • Common peroneal nerve near fibular neck and posterior tibial nerve in tarsal tunnel are commonly involved in the lower limb.
  • 64. • Carpal tunnel syndrome - most common entrapment neuropathy. • Occurs due to compression of the median nerve in the carpal tunnel bounded by the carpal bones and the flexor retinaculum. • The diagnosis is based on the patient's history of sensory and motor symptoms in median nerve distribution and clinical examination findings. • USG is comparable with nerve conduction studies in the diagnosis of carpal tunnel syndrome. • It shows the classic triad of (Buchberger et al) :- – enlargement of the nerve at the level of distal radius and proximal carpal tunnel – flattening of the nerve in distal carpal tunnel and – palmar bowing of the flexor retinaculum.
  • 65. • A cross-sectional area of the median nerve proximal to the tunnel inlet more than 10 mm2 is abnormal. • The abrupt change in nerve caliber at the entrance of carpal tunnel is called “notch sign”. • The nerve may show a homogeneous hypoechoic appearance with loss of fascicular echopattern • A contralateral comparison usually helps in detecting subtle signs to reach the diagnosis.
  • 66. Longitudinal USG image of Normal median nerve proximal to and in the carpal tunnel. T: Flexor tendons in the carpal tunnel; MN: Median nerve
  • 67. (A) Longitudinal USG image shows enlargement of the median nerve at carpal tunnel inlet and outlet in carpal tunnel syndrome. (B) Axial USG image shows increase in cross-sectional area of the median nerve proximal to the tunnel. It is 12.6 mm2 .Normal being less than 10 mm2
  • 68. (A) Longitudinal USG image reveals abrupt change in the caliber of median nerve at the entrance of carpal tunnel (Notch sign) in carpal tunnel syndrome. (B) Intraoperative image confirming the ultrasound findings
  • 70. REFERENCES • Transcranial Doppler Ultrasound: Technique and Application : Sushmita Purkayastha, Farzaneh Sorond : Seminars in Neurology 2012;32:411–420. • Textbook of Emergency Neuroradiology : T Scarabino • Role of ultrasound in evaluation of peripheral nerves : Ashwin D et al : Indian J Radiol Imaging. 2014 Jul-Sep; 24(3): 254–258. • High-Resolution Sonography of Lower Extremity Peripheral Nerves: Anatomic Correlation and Spectrum of Disease : Siegfried Peer et al : J Ultrasound Med 21:315–322, 2002 • Sonography of Peripheral Nerve Pathology : R. M. Stuart et al : American Journal of Roentgenology. 2004;182: 123-129. • Bradley’s Neurology in clinical Practice : 7th edition