Clots in Tots: Imaging of Pediatric VasoOcclusive Disorders

1
Clots in TotsImaging of Pediatric
Vaso-Occlusive Disorders

• R. Paul Guillerman, MD, FAAP
• Department of Radiology

2
Venous Thromboembolism (VTE) in Children and
Adolescents

• Peak thrombotic risk in infancy and adolescence
• Central venous catheter most common risk factor
• 95 occur in serious conditions such as cancer
  (especially ALL treated with asparaginase),
  trauma, congenital heart disease surgery
  (especially Fontan), hemoglobinopathy,
  antiphospholipid syndrome, nephrotic syndrome,
  vascular malformations, obesity, immobilization

Tormene Semin Thromb Hemost 2006, Sandoval J Vasc
Surg 2008, Monagle Chest 2008
3
VTE in Children and Adolescents

• Genetic prothrombotic disorder in 13-60
• Deficiencies of antithrombin III, protein C,
  protein S
• Mutations of factor V Leiden, factor II,
  methylene-tetrahydrofolate reductase
• Hyperhomocysteinemia
• Growing recognition of acute infection as a risk
  factor
• Recurrent in 8, more commonly in older and
  thrombophilic children

Tormene Semin Thromb Hemost 2006, Sandoval J Vasc
Surg 2008, Monagle Chest 2008
4
Ultrasonography (US) for Deep Venous Thrombosis
(DVT)

• Cheap, easy to perform, without procedural risk,
  and highly sensitive for lower extremity and
  jugular clot
• Specificity and specificity 94 for proximal LE
  DVT in pooled meta-analysis of adult studies
• Less sensitive for clot in the distal lower
  extremities, pelvis and upper intrathoracic veins

Babyn Pediatr Radiol 2005, Goodacre BMC Med Imag
2005
5
Venous Doppler US of Lower Extremity DVT
6
MR Venography (MRV) for DVT

• Superior visualization of the IVC and deep pelvic
  veins compared to ultrasound, particularly in
  large patients
• Sensitivity 92 (94 proximal DVT, 62 distal
  DVT), specificity 95 in pooled meta-analysis of
  adult studies
• No ionizing radiation exposure
• Can be diagnostic without use of intravenous
  contrast
• Less readily available than US

Sampson Eur Radiol 2007
7
Normal MRV
8
MRV of Iliofemoral DVT
12 yo girl with right lower extremity swelling
and pain
9
VTE Related to Central Vascular Catheters (CVC)

• Accounts for 90 of neonatal VTE (excluding renal
  vein)
• Risk highest with UVC (29), followed by PICC
  (8), port (4), and tunneled catheter (3)
• Usually asymptomatic, but can lead to line
  sepsis, venous occlusion and post-thrombotic
  syndrome
• Most common source of PE, and can result in
  paradoxic emboli with catheter removal,
  especially in neonates
• Accounts for higher incidence of upper extremity
  DVTs in children compared to adults

McCloskey Pediatr Nurs 2002, Barnacle Pediatr
Radiol 2008, Monagle Chest 2008
10
Upper Extremity DVT and CVC

• Higher risk if left-side, subclavian,
  percutaneous insertion
• SVC syndrome risk increased if tip not in RA or
  lower SVC
• Difficult to diagnose with imaging
• US sensitivity only 37 (misses many SVC,
  brachiocephalic, and subclavian clots)

Male Thromb Haemostas 2002
11
Fibrin Sheaths

• Form along a majority of catheters
• Can lead to withdrawal occlusion of the catheter,
  infectious seeding, or drug extravasation

Barnacle Pediatr Radiol 2008
12
Post-Thrombotic Syndrome

• Chronic venous hypertension resulting from
  valvular incompetence and outflow obstruction
• Extremity pain, swelling, skin discoloration, and
  ulceration
• Portal HTN, communicating hydrocephalus,
  chylothorax
• Develops after DVT in 20 of children at median
  interval of 3 months, and in 60 after DVT
  related to CVC or thrombophilia
• Incidence similar with asymptomatic and
  symptomatic DVT
• Risk factors include gt 48 hr delay in treatment
  initiation, obstruction of gt 50 luminal diameter
  at presentation, plasma factor VIII or D-dimer
  elevation, and recurrence or lack of resolution
  of DVT
• Asymptomatic DVT in 35-73 of pediatric ALL
  patients by US
• Imaging reveals collaterals, intravenous reflux,
  vessel wall thickening, or luminal occlusion

Monagle Pediatr Res 2000, Goldenberg N Engl J Med
2004, Kuhle J Thromb Haemo 2008, Sharathkumar J
Pediatr Hematol Oncol 2008
13
Pulmonary Embolism (PE) in Children

• Average delay in diagnosis is 7 days
• Clinical likelihood models developed for adults
  not validated in children
• d-dimer sensitivity as low as 60, compared to
  87-98 in adults

Goldenberg NEJM 2004, Babyn Pediatr Rad 2005,
Rajpurkar Thromb Res 2006
14
CXR for PE

• Often normal or shows nonspecific abnormalities
  such as subsegmental atelectasis or pleural
  effusion
• Wedge-shaped pleural-based air-space opacities
  (pulmonary infarcts) and regional hypoperfusion
  are more specific findings on CXR but much less
  frequently encountered

Lake Semin Ultrasound CT MRI 2006
15
Conventional Pulmonary Angiography for PE

• Historical gold standard
• Invasive, but lower morbidity (5) and mortality
  (lt1) than anticoagulation
• Very high sensitivity and negative predictive
  value (98-100) in adult studies
• Poor interobserver reliability (33-66) for
  subsegmental clots

Henry Chest 1995, Diffin AJR 1998, Stein
Radiology 1999, Babyn Pediatr Radiol 2005
16
US for PE

• Documentation of DVT often obviates the need for
  specific lung evaluation, as anticoagulation
  treatment is generally the same
• DVT present in 30-60, with higher incidence of
  upper venous system involvement than in adults
• Most children who die from PE have no detectable
  DVT

Stein J Pediatr 2004, Babyn Ped Rad 2005
17
Ventilation/Perfusion (V/Q) Scan for PE

• Perfusion scintigraphy performed most commonly
  with technetium-99m macro-aggregated albumin
  (MAA)
• Ventilation scintigraphy most commonly performed
  with Tc99m-DTPA aerosol or Xenon-133 gas
• Lower radiation dose than CT or conventional
  angiography
• Diagnostic efficacy in adults well defined by
  PIOPED I study
• 96 PPV if high probability scan and clinical
  assessment, 96 NPV if low probability scan and
  clinical assessment

PIOPED Investigators JAMA 1990, Babyn Pediatr
Radiol 2005
18
V/Q Scan for PE

• Poor interobserver reliability in adults
• Inconclusive (not high probability or normal/near
  normal) in 75 of adults in PIOPED I
• Diagnostic (high probability or normal/near
  normal) in majority of adults with suspected PE
  and normal CXR
• Inconclusive study less common in children,
  except those with pre-existing lung disease or
  congenital heart disease

PIOPED Investigators JAMA 1990, Forbes Clin
Radiol 2001
19
Perfusion-Only Scan for PE

• Applicability of PIOPED diagnostic criteria to
  children unclear, but perfusion defects more
  likely to represent clot in children
• Ventilation scan difficult to obtain in infants
  and toddlers
• Omitting ventilation scan reduces radiation dose
  and cost without compromising diagnostic efficacy
• Recommended for follow-up, children, females of
  reproductive age, particularly if CXR normal

PIOPED Investigators JAMA 1990, Stein Am J
Cardiol 1992, Miniati Am J Resp Crit Care Med 1996
20
Acute PE on Tc-99m MAA Lung Perfusion Scan
17 yo girl with SLE, lupus anticoagulant
positive, elevated D-dimer
21
CT Pulmonary Angiogram (CTPA) for Pulmonary
Embolism

• Diagnostic efficacy enhanced with thin-slice MDCT
  and multiplanar image reconstructions
• Sensitivity 83-100, specificity 89-97
• Now the initial study of choice in adults, with
  higher interobserver reliability and fewer
  inconclusive exams compared to V/Q scans
• Other advantages over V/Q include direct thrombus
  visualization and identification of alternative
  diagnoses
• e.g. pneumonia, pleural disease, pericarditis,
  aortic dissection

Remy-Jardin Radiology 2007
22
CTPA Technique

• No contraindication to iodinated contrast media
• Prior severe adverse reaction
• Renal insufficiency
• Rapid intravenous contrast injection with
  unobstructed route to pulmonary circulation
• At least 3 ml/sec and at least 22G IV, preferably
  antecubital
• Avoid subclavian/SVC thrombosis or central
  vascular catheter
• Breath-hold at end-expiration
• Chest coverage 5 cm/sec for 16-slice CT, 10
  cm/sec for 64-slice CT
• 2-5 sec required to scan through chest of typical
  adolescent
• Preschoolers generally unable to reliably
  breath-hold
• Inspiration leads to contrast dilution and
  suboptimal enhancement

Wittram AJR 2007
23
Normal CTPA
24
Contrast Delivery Impaired by Brachiocephalic
Vein Stenosis
18 yo girl with cough, back pain
25
Contrast Dilution by Inspiratory Influx of
Unopacified Blood
Expiratory
Inspiratory
Bhalla Eur J Radiol 2007
26
CTPA of Acute PE
17 yo girl with SLE, lupus anticoagulant
positive, elevated D-dimer
27
CTPA of Acute PE
17 yo girl with SLE, lupus anticoagulant
positive, elevated D-dimer
28
CTPA of Acute PE
17 yo girl with SLE, lupus anticoagulant
positive, elevated D-dimer
29
CTPA of Chronic PE

• Small, thick-walled pulmonary artery
• Webs
• Enlarged bronchial artery collaterals

Wittram Radiographics 2004
30
CTPA of Pulmonary Hypertension and Right
Ventricular Strain

• Right ventricular dilation
• Deviation of interventricular septum toward the
  left ventricle
• Reflux of contrast into the hepatic veins
• Pulmonary embolism burden gt 60

15 yo boy with chronic PE
31
PIOPED II StudyDiagnostic Efficacy of CTPA

• Analyzed results on 824 patients at least 18 yo,
  92 outpatient
• Central readings of 4-16 row MDCT
• Specificity 96
• Sensitivity 83 (90 with combined CTA and lower
  extremity CT venography)
• Primarily misses small peripheral subsegmental
  clots
• Inconclusive in 6 of CTA and 11 of CTA-CTV

Stein NEJM 2006
32
PIOPED II StudyImportance of Clinical Assessment

• In those with low probability clinical
  assessment, CTA NPV 96, PPV 58 (25 if
  subsegmental, 68 if segmental, 97 if lobar or
  main PA)
• In those with moderate probability clinical
  assessment, CTA NPV 89, PPV 92
• In those with high probability clinical
  assessment, CTA NPV 60 (82 with CTV), PPV 96

Stein NEJM 2006
33
Outcomes Predicted by CTPA

• lt 2 incidence of thromboembolic events (PE or
  DVT) in adults not anticoagulated because of
  negative CTA
• 0.07 NLR and 99 NPV compares to 76-88 NPV of
  negative or low probability V/Q scan

Gosselin Radiology 1998, Quiros JAMA 2005, Eyer
AJR 2005, Perrier NEJM 2005
34
Outcomes Predicted by CTPA

• Isolated subsegmental PE (ISSPE) in adults
• Found in 1.5 with unsuspected PE, in 4-6 with
  suspected PE, and in 20-25 with PE
• Recurrent PE rare if no DVT, even if not
  anticoagulated
• Outcome may be better if not anticoagulated,
  since 1 fatality rate and 7 major complication
  rate per year of anticoagulation treatment
• Anticoagulation for subsegmental PE still
  recommended in those with coexisting acute DVT,
  poor cardiopulmonary reserve, or thrombophilia

Levine Chest 1995, Eyer AJR 2005, Remy-Jardin
Radiology 2007
35
Treatment and Outcome of Massive PE

• For massive PE with circulatory collapse,
  immediate thrombolysis is recommended, and
  peripheral administration is as effective as
  catheter-directed
• Pulmonary arterial occlusion gt 60 (12 segmental
  PA equivalents) on CTPA is a predictor of
  mortality in adults

British Thoracic Society Thorax 2003, Wu
Radiology 2004
36
PIOPED II RecommendationsD-Dimer Rapid ELISA
Pathway
37
PIOPED II RecommendationsLow Probability
Clinical Assessment
38
PIOPED II RecommendationsModerate Probability
Clinical Assessment
39
PIOPED II RecommendationsHigh Probability
Clinical Assessment
40
Risk Assessment in Suspected Acute PE

• Adherence to published pretest probability
  guidelines is 23, similar to adherence to
  guidelines for other conditions such as asthma
  and hypertension
• Younger physicians less likely to calculate a
  pretest probability
• High efficacy and widespread availability of CTPA
  has led to a dramatic increase in use and
  decrease in fraction of positive exams
• Only 3 of CTPA positive for PE at Mallinckrodt
  in 2006

Weiss Academ Radiol 2008
41
PIOPED II and Fleischner Society Recommendations
for Patients with Allergy to Iodinated Contrast
Media

• D-dimer testing with clinical assessment is
  recommended to exclude pulmonary embolism
• Patients with mild iodine allergies may be
  treated with steroids prior to CT imaging
• Venous US and pulmonary scintigraphy are
  recommended as alternative diagnostic tests in
  patients with severe iodine allergy
• Serial venous US examinations and
  gadolinium-enhanced CT or MRI angiography are
  options

42
PIOPED II and Fleischner Society Recommendations
for Patients with Renal Insufficiency

• D-dimer testing with clinical assessment is
  recommended to exclude pulmonary embolism
• Venous US is recommended, and if results are
  positive, treatment is indicated
• Pulmonary scintigraphy is recommended if venous
  US results are negative
• Serial venous US examinations are an option

43
PIOPED II and Fleischner Society Recommendations
for Women of Reproductive Age

• If D-dimer rapid ELISA results are positive,
  pulmonary scintigraphy is recommended by 31 of
  PIOPED II investigators as the next imaging test,
  but most (69) recommend CT angiography
• Fleischner Society recommends venous US and
  perfusion scintigraphy
• CT angiography with venous US is an acceptable
  alternative

44
V/Q Scan Unclear Medicine ?

• Definitive positive or negative V/Q scan reading
  possible in nearly 90 of patients with normal or
  near normal CXR
• In PIOPED II, 1/4 of V/Q scans were nondiagnostic
  (intermediate or low probability) while 3/4 were
  definitively positive (high probability) or
  negative (very low probability, or normal) for a
  sensitivity of 77 and specificity of 98
• Sensitivity and specificity very similar to CTPA
  when nondiagnostic studies excluded
• In PIOPED II, slightly greater than 1/2 of V/Q
  scans interpreted as very low probability, and
  1/3 had both low probability clinical assessment
  and very low probability V/Q scan reading
• If low probability clinical assessment, NPV 97

Gottschalk Semin Nuc Med 2002, Gottschalk J Nuc
Med 2007, Sostman Radiology 2008
45
When is V/Q Preferred over CTPA?

• Renal insufficiency
• History of severe adverse reaction to contrast
• Women of reproductive age, especially if low
  probability clinical assessment for PE
• Children, especially if clear CXR and no
  underlying cardiopulmonary disease

46
British Thoracic Society Recommendations

• V/Q scan can be performed as a first-line imaging
  test provided that
• CXR is normal
• No significant concurrent cardiopulmonary disease
  is present
• Standardized reporting criteria are used
• Non-diagnostic results are followed by further
  imaging

British Thoracic Society Thorax 2003
47
Evaluation and Management of PE in Children and
Adolescents

• Dearth of publications on diagnostic efficacy of
  imaging and optimal treatment
• Efficacy of CTPA in adolescents likely very
  similar to adults
• Technique demands compromise CTPA quality in
  young children and likely reduce efficacy and
  increase frequency of nondiagnostic exams
• D-dimer assay of limited value for screening
  children due to low sensitivity for VTE, and
  adult PIOPED II algorithm not appropriate
• Radiation dose from increased use of CTPA is a
  concern

48

• 11th Report on Carcinogens, 2005
• X-radiation and gamma radiation listed as known
  to be human carcinogens

49
Comparative Imaging Doses

• Chest CTPA effective dose 60-500 CXR
• Chest CTPA breast dose 6-8 mammograms

50
Lifetime Attributable Risk of Cancer from a
Pediatric Chest CTPA (4 mSv)

• Assuming linear no-threshold model and BEIR VII
  preferred estimates for solid tumor and leukemia
  for a 10 year-old
• Incidence Female 1/960, Male 1/1750
• Mortality Female 1/2275, Male 1/3500
• Very similar to the risk of dying from a fire or
  drowning during childhood

51
Background Radiation Equivalent Time (BERT)

• Average natural background radiation exposure in
  the US is 3 mSv/yr or about 0.01 mSv/day
• A typical pediatric chest CTPA incurs about 1
  year of BERT
• A typical CXR incurs about 1 day of BERT

52
Pediatric Chest CTPA (4 mSv) Activity Equivalent
Mortality Risk

• Smoking 500 cigarettes
• Riding 1,100 miles on a motorcycle
• Riding 14,000 miles in a car
• Flying 360,000 miles on commercial airliner

53
Loss of Life Expectancy

• Smoking at least 1 pack of cigarettes/day 4-7
  years
• Agriculture occupational accident 320 days
• Construction occupational accident 227 days
• Motor vehicle accident 207 days
• Age-averaged median life expectancy decrease of
  about 0.5 day/mSv noted for A-bomb cohort
• Chest CTPA in a child associated with 4 days loss
  of life expectancy from radiation

Cohen Health Phys 1991, Cologne Lancet 2000
54
Framing Risks

• Your childs risk from the chest CT scan is
• 99.97 chance of not getting a fatal cancer from
  the CT
• The same as 1 year of natural background
  radiation
• 1/3000 chance of getting a fatal cancer
• Similar to dying from drowning or a fire
• Losing a few days of life expectancy
• Equal to smoking about 500 cigarettes
• Similar radiation dose as being 3 miles away from
  the Hiroshima atomic bomb blast

55
ALARA (As Low As Reasonably Achievable) Principle

• Imaging technique is selected to incur the
  minimum radiation dose needed to make the
  diagnosis rather than to maximize image quality
• Courts have ruled that ALARA and not the
  regulatory exposure limit is the appropriate
  standard of care
• Less margin of error for obtaining images of
  diagnostic quality

56
Why Not Just Reduce CT Radiation Dose?

• The lower the dose, the lower the image
  signal-to-noise and the lower the image quality
• The lower the image quality the greater the
  chance of a misdiagnosis or inconclusive exam
• With increased patient size, a marked increase in
  dose is required to achieve same image quality

57
Obesity is a Big Problem
Excessive image noise simulating PE
Wittram Radiographics 2004
58
Suggested Imaging Algorithm for Suspected PE/DVT
in Children
Babyn Pediatr Radiol 2005
59
IVC Filters in Pediatric Patients

• Safety and efficacy in children are undefined at
  present
• Indications in adults include VTE and a
  contraindication to or failure of anticoagulation
• Technically feasible in children as young as 6
  years, but no current filters are designed
  specifically for pediatric use
• Long-term complications include thrombosis,
  filter migration, filter fracture, and IVC wall
  penetration
• Can monitor with ultrasound

Reed Cardiovasc Intervent Radiol 1996, Cahn J
Vasc Surg 2001, Raffini Pediatr Blood Cancer 2008
60
Retrieval of IVC Filter

• Retrievable filters favored in children to avoid
  long-term complications

Reed Cardiovasc Intervent Radiol 1996 Raffini
Pediatr Blood Cancer 2008
61
Not All PE are Thrombotic
2 yo boy with adrenal cortical carcinoma, IVC
invasion, and tumor emboli

• Tumor emboli in children or adolescents most
  common with Wilms tumor, hepatoblastoma, adrenal
  carcinoma, renal cell carcinoma

62
Fat Emboli

• Usually manifests 1-3 days after long bone or
  pelvic fracture
• Pulmonary microvascular obstruction and chemical
  pneumonitis, producing ground glass nodules

Bhalla Eur J Radiol 2007, Nucifora JCAT 2007
63
Septic Emboli
16 yo girl with fever, sore throat

• In 1936 (pre-antibiotic era), Lemierre reported
  pharyngeal infection followed by thrombophlebitis
  of the internal jugular vein and septicemia
• Involvement of lungs in 79-100, joints in 13-27

64
Lemierres Syndrome

• Predominant pathogen is a Gram - anaerobic
  bacillus, Fusobacterium necrophorum, but is
  frequently polymicrobial
• Also Actinomycetes, Staph, Strep
• Most common in teenage males
• No longer the forgotten disease
• Rising incidence may be related to public health
  measures restricting prescription of antibiotics
  for sore throat
• Thrombophilia (e.g. APLA, elevated FVIII
  activity) is likely an epiphenomenon since
  present in all at diagnosis, but rarely
  persistent
• Slow response to antibiotics
• 8 mortality

Goldenberg Pediatrics 2005, Syed Laryngoscope 2007
65
Lemierres Syndrome Post-Thrombotic Syndrome

• 44 have persistent jugular vein thrombosis at
  3-6 months
• Associated with completely occlusive thrombus and
  lack of anticoagulation

Persistent internal jugular occlusion despite
Lovenox
66
Invasive Community-Acquired MRSA Infection with
DVT and Septic Emboli
67
Staphylococcal Septic Thrombophlebitis

• Deep venous thrombosis complicates 7-8 of cases
  of osteomyelitis from community acquired
  -Staphylococcus aureus (CA-SA)
• DVT complicates nearly 1/3 of cases of severe
  invasive CA-SA infection
• Associated with Panton-Valentine leukocidin,
  elevated ESR/CRP/D-dimer/fibin split products
• Typically near site of osteomyelitis
• 20 mortality, septic pulmonary emboli often
  present

Gonzalez et al Pediatrics 2006, Browne Pediatr
Radiol 2008
68
Dural Venous Sinus Thrombosis

• Predominantly seen in neonates and young infants
• Seizures, lethargy, headache, signs of increased
  intracranial pressure, or focal neurologic
  deficits
• Dehydration, thrombophilia, sepsis, sinomastoid
  infection, hyperleukocytosis, asparaginase, iron
  deficiency anemia

5 yo boy on pegaspargase for ALL
Tormene Semin Thromb Hemost 2006, Dinndor
Oncologist 2007
69
Dural Venous Sinus Thrombosis

• Complicating cortical vein thrombosis and
  hemorrhagic infarctions predict worse outcome
• Doppler US, CTV, MRV can be used for diagnosis
  and for monitoring for propagation or
  recanalization

Tormene Semin Thromb Hemost 2006, Dinndor
Oncologist 2007
70
Antiphospholipid Syndrome (APS)

• Systemic autoimmune disorder with venous or
  arterial thromboses and elevated titers of
  antiphospholipid antibodies (aPL) such as the
  lupus anticoagulant (LA), anticardiolipin
  antibody (aCL), and anti-ß2-GPI antibody
• Can involve any vessel and organ system
• DVT, PE, stroke, Budd-Chiari, livedo reticularis,
  MAHA
• Consider if vascular thrombosis without
  alternative explanation, particularly if
  recurrent or asymptomatic
• May be primary or associated with an underlying
  systemic disease, especially SLE

Ravelli Rheum Dis Clin N Am 2007
71
Tc-99m MAA Lung Perfusion Scan in Girl with Lupus
and Chest Pain
16 yo girl with lupus and chest pain
72
SVC Syndrome from Thrombosis

• Associated with central vascular catheters,
  malignancy, thrombophilia, cardiac surgery
• Collateral drainage may include Sappey veins to
  liver

16 yo girl with lupus and chest pain
Kwong Clin Exp Rheumatol 1994, Muramatsu Clin Nuc
Med 1994, Genchellac JCAT 2007
73
SVC Syndrome from Tumor Compression

• Most common with lymphoma, T-cell ALL
• Complicates central vascular catheter placement

T-cell ALL with airway compression and SVC
syndrome
74
Portal Vein Thrombosis

• Usually silent until GI bleed, splenomegaly, or
  cholestasis occurs, or until detected by routine
  surveillance imaging
• May be a cause or consequence of portal
  hypertension
• Associated with thrombophilias, umbilical venous
  catheterization, omphalitis, pancreatitis, liver
  transplantation, splenectomy, tumor, portal
  phlebitis
• gt 95 sensitivity/specificity of US, CT, or MRI

Peter J Gastroenterol Hepatol 2003 Schettino J
Pediatr 2006, Soyer J Pediatr Surg 2006
75
Acute Portal Vein Thrombosis

• Thrombus may be anechoic and indistinguishable
  from flowing blood unless Doppler performed
• False-positive Doppler possible with sluggish flow

76
Chronic Portal Vein Thrombosis

• Cavernous transformation of the portal vein
• Progressive portal vein fibrosis
• Periportal collaterals with reduced flow velocity
• Portal-systemic shunting
• Varices
• Splenomegaly
• Ascites
• Portal hypertensive biliopathy

77
Chronic Portal Vein Thrombosis with Cavernous
Transformation, Splenomegaly, and Spontaneous
Splenorenal Shunt
78
Chronic Portal Vein Thrombosis with Cavernous
Transformation and Esophagogastric Varices

• CT or MR angiography superior to US for depiction
  of portosystemic shunts and varices

79
Chronic Portal Vein Thrombosis with Portal
Hypertensive Biliopathy

• Bile duct stenosis and tortuosity leading to
  biliary obstruction and cholestasis
• Due to bile duct ischemia and biliary compression
  associated with cavernous transformation of the
  portal vein
• Can be diagnosed with conventional or MR
  cholangiography
• Similar appearance to Carolis disease or
  sclerosing cholangitis

9yo boy with PHB
El-Matary Eur J Pediatr 2008
80
Extensive Portomesenteric Thrombosis

• Occurs with thrombophilias such as
  myeloproliferative disorders and paroxysmal
  nocturnal hemoglobinuria
• Intravascular tumor invasion distinguished from
  bland thrombus by vascularity and enhancement of
  the former

2 yo boy with hepatocellular carcinoma
81
Splenic Vein Thrombosis

• Usually asymptomatic but increasingly recognized
  due to increased use of advanced imaging
• Complication of pancreatitis or hypercoagulable
  states
• Increased risk with pseudocysts
• Leads to sinistral portal hypertension
• Patent portal vein and preserved liver function
• Isolated gastric varices
• May require splenectomy for treatment of variceal
  bleeding

Heider Ann Surg 2004
82
Splenic Vein Thrombosis and Sinistral Portal
Hypertension
16 yo boy with pancreatitis, pseudocyst and
gastric varices
83
Budd-Chiari Syndrome

• Classic triad of abdominal pain, hepatomegaly and
  ascites described by Budd in 1845
• Hepatic venous outflow obstruction at level of
  major hepatic veins or IVC related to
• Hypercoagulable states (especially
  myeloproliferative disorders with acquired Janus
  kinase 2 (JAK2) V617F mutation and paroxysmal
  nocturnal hemoglobinuria)
• Membraneous web (more common in Asians may be
  sequela of thrombus rather than congenital)
• Liver transplantation
• Tumor
• Young children typically present at irreversible
  late stage

Chaubal JUM 2006, Horton Liver Int 2008
84
Imaging Findings of Budd-Chiari Syndrome

• Acute hepatomegaly, inhomogeneous liver
  enhancement
• Subacute or chronic atrophy of liver periphery,
  caudate lobe hypertrophy, regenerative liver
  nodules
• Absent or abnormal hepatic vein or IVC flow
• Intrahepatic and extrahepatic collaterals
• Ascites
• Portal hypertension

Chaubal JUM 2006, Horton Liver Int 2008
85
Budd-Chiari Syndrome from Suprahepatic IVC
Stenosis
86
Budd-Chiari Syndrome from Thrombosis of IVC/HV
Confluence
87
Budd-Chiari Syndrome from Tumor Invasion of
Hepatic Veins and IVC
a
b
Infant with hepatoblastoma invading hepatic vein,
IVC and right atrium
88
Hepatic Veno-Occlusive Disease (HVOD)

• Endothelial injury and sloughing leading to small
  hepatic vein obstruction and fibrosis in hepatic
  sinusoids
• Etiologies
• Busulfan-containing conditioning regimens for
  hematopoietic cell transplantation (usually
  within 3 weeks)
• Chemotherapy
• Solid organ transplant immunosuppresion
  (azathioprine)
• Plant-derived pyrrolizidine alkaloids in herbal
  teas and medicines, especially comfrey
• Radiation
• Weight gain, jaundice associated with higher
  mortality
• Imaging findings nonspecific

Cesaro Haematologica 2005, Cheuk Bone Marrow
Transpl 2007, McCarville Pediatr Radiol 2001
89
HVOD in Infant 3 Weeks After Bone Marrow
Transplantation for HLH

• Hepatosplenomegaly
• Ascites
• Gallbladder wall thickening
• Patent major hepatic veins
• High resistance hepatic arterial flow
• Decreased or reversed portal venous flow

90
Response to Defibrotide Therapy in Infant with
HVOD

• Traditional management consists of supportive
  care with fluid restriction and diuretics
• Defibrotide effective in prophylaxis and
  treatment in children

Qureshi Pediatr Blood Canc 2008
91
Pulmonary Veno-Occlusive Disease (PVOD)

• Histologic hallmarks of PVOD are webs,
  recanalized thrombosis, and intimal fibrosis
  within the post-capillary pulmonary venules
• Associated with infection, genetic factors, toxic
  exposures, thrombotic diathesis and autoimmune
  disorders
• Critical to distinguish PVOD from IPAH
• Prostacyclin is an effective treatment for
  idiopathic pulmonary arterial HTN but can be
  harmful in PVOD, leading to fulminant pulmonary
  edema

Resten Eur Radiol 2005
92
High-Resolution Chest CT of PVOD

• Poorly defined centrilobular opacities
• Smooth septal thickening
• Pleural effusion
• No enlargement of central pulmonary veins or left
  atrium

Resten Eur Radiol 2005
93
Neonatal Renal Vein Thrombosis

• Most common noncatheter-related thrombosis in
  infancy
• Typically presents within the first week of life
• Usually only one or two of the classic triad of
  macroscopic hematuria, palpable mass,
  thrombocytopenia
• Thrombophilia in 50, prematurity or perinatal
  asphyxia in 30, maternal diabetes in 8,
  dehydration in lt 2
• 2/3 male and 2/3 involve left side
• 44-60 involve the IVC, 25 bilateral, 15
  associated with adrenal hemorrhage

Winyard Arch Dis Child Fetal Neon Ed 2006 Lau
Pediatrics 2007 Elsaify Abdom Imaging 2008
94
US of Neonatal RVT

• Imaging appearance depends on severity and timing
  and is neither sensitive nor specific
• Begins in small intrarenal veins and propagates
  to the main renal veins and IVC
• Monitoring for extension into the IVC is
  recommended
• 71 of involved kidneys become atrophic
• Sequelae include chronic renal insufficiency and
  HTN
• Anticoagulation may not improve outcome compared
  to supportive measures alone

Winyard Arch Dis Child Fetal Neon Ed 2006 Lau
Pediatrics 2007 Elsaify Abdom Imaging 2008
95
Neonatal Renal Vein Thrombosis

• Acutely, enlarged kidney with loss of
  corticomedullary differentiation and possible
  echogenic interlobular streaks
• Negative correlation between renal length and
  outcomes

96
Neonatal Renal Vein Thrombosis

• Doppler US may reveal clot or diminished venous
  blood flow
• If thrombosis is restricted to the small
  intrarenal veins, blood flow in the main renal
  vein may appear normal, but there may be an
  increase of flow resistance in the renal arteries

97
Renal Artery Stenosis

• Responsible for 5 - 25 of cases of pediatric
  hypertension
• Second only to coarctation as a surgically
  correctable cause of hypertension
• Can be idiopathic or secondary to fibromuscular
  dysplasia, mid-aortic syndrome,
  neurofibromatosis, Takayasus arteritis,
  radiation injury, or trauma from umbilical
  arterial catheterization
• US has low sensitivity and specificity
• CTA or MRA increasingly requested for evaluation

98
Normal Renal CTA
99
Renal Artery Stenosis from Fibromuscular Dysplasia
100
Imaging for Renal Artery Stenosis

• Even with meticulous technique, CTA and MRA have
  low sensitivity for stenoses of small branch
  renal arteries
• Hypertensive children with renal artery stenosis
  without co-morbid conditions usually (75) have
  stenosis of a single branch renal artery
• In patients with high clinical suspicion of
  renovascular HTN, conventional angiography
  advocated because of its superior sensitivity for
  branch renal artery stenosis, cost-effectiveness,
  and option for immediate percutaneous
  transluminal renal angioplasty

Vo Pediatr Radiol 2006, Helvoort-Postulart
Radiology 2007
101
Branch Left Renal Artery Stenosis on MRA and
Conventional Angiography
10 yo girl with HTN
102
Severe Left Renal Artery Stenosis Occult to
Doppler Sonography
10 yo girl with HTN
103
Severe Left Renal Artery Stenosis Appearing as
Complete Occlusion on MRA
10 yo girl with HTN
104
Severe Left Renal Artery Stenosis on Digital
Subtraction Angiography
10 yo girl with HTN
105
Severe Left Renal Artery Stenosis Post-Balloon
Angioplasty
10 yo girl with HTN
106
Mid-Aortic Syndrome

• Segmental narrowing of the upper abdominal aorta
  and its proximal major branches (renal arteries,
  SMA)
• Usually diagnosed in young adults, but may
  present in infancy, and should be considered a
  cause of unexplained HTN in a child
• May occur as an isolated entity, or in
  association with Alagille syndrome, Williams
  syndrome, rubella, neurofibromatosis, Takayasus
  arteritis, and retroperitoneal fibrosis
• Treated by medical therapy, balloon angioplasty,
  stent placement, nephrectomy, or surgical
  reconstruction

Panayiotopoulos Br J Surg 1996
107
Mid-Aortic Syndrome
12 yo boy with HTN
108
Takayasus Arteritis

• Arterial inflammation with resulting stenosis or
  aneurysm
• Most commonly involves aorta, renal, subclavian,
  carotid and pulmonary arteries
• Hypertension (89), absent pulses (58), and
  bruits (42)
• Headache (84), abdominal pain (37),
  claudication of extremities (32), fever (26),
  and weight loss (10)

16 yo boy with loss of left arm pulses
109
Takayasus Arteritis

• US is cheap, safe, and readily available but
  assesses fewer vessels than CT or MR angiography
• Vessel wall hyper-enhancement, thickening and FDG
  uptake suggest active inflammation
• FDG-PET is the most sensitive imaging modality

Pipitone Rheumatology 2008
110
Takayasus Arteritis

• Diagnostic delay can lead to catastrophic
  complications such as stroke or MI
• Biannual MRA or CTA helpful to screen for new
  aortic aneurysms or arterial stenoses
• Imaging signs of vascular inflammation do not
  necessarily predict subsequent stenosis or
  aneurysm and may persist despite clinical
  remission
• Most patients require chronic immunosuppression
  and revascularization with percutaneous
  transluminal angioplasty or bypass grafting is
  reserved for cases of critical organ ischemia or
  severe extremity claudication

Cakar J Rheumatol 2008, Koening Curr Treat
Options Cardiovasc Med 2008