Imaging in Cystic Fibrosis

1. DR. AMEEN RAGEH

2. INTRODUCTION
Is an inherited multisystem disorder of children and
adults
It is the most common life-limiting recessive genetic
trait among white persons.
Is responsible for most cases of exocrine pancreatic
insufficiency in early life and is the major cause of
severe chronic lung disease in children.
Responsible for many cases of salt depletion, nasal
polyposis, pansinusitis, rectal prolapse, pancreatitis,
cholelithiasis, and insulin-dependent
hyperglycemia.

3. GENETIC
The cystic Fibrosis gene was isolated in
1989 and mapped to chromosome 7.
More than 1300 different mutations of this
gene have been identified, all of which
cause a defect in chloride transport
across the cell membrane;
The severity of chloride channel
dysfunction varies widely with different
mutations.

4. PATHOPHYSIOLOGY
 Dysfunction of the cystic fibrosis transmembrane
conductance regulator protein (CFTR).
 CFTR is expressed largely in epithelial cells of airways, the
gastrointestinal tract (including the pancreas and biliary
system), the sweat glands, and the genitourinary system.
 It functions as a chloride channel and has other regulatory
functions
 The alteration in chloride transport is associated with
production of abnormally thick secretions in glandular
tissues. The lung bronchioles and pancreatic ducts are
primarily affected, often resulting in progressive destruction
of these organs

6. PATHOPHYSIOLOGY
The result is that these secretions are retained and
obstruct airways, starting with those of the smallest
caliber, the bronchioles.
In the pancreatic and biliary ducts (and in the vas
deferens), leading to desiccation of proteinaceous
secretions and obstruction.
The function of sweat gland duct cells is to absorb
rather than secrete chloride, salt is not retrieved
from the isotonic primary sweat as it is transported
to the skin surface; chloride and sodium levels are
consequently elevated

7. Sequelae
Chronic infection in CF is limited to the airways. A
likely explanation for infection is a sequence of
events starting with failure to clear inhaled bacteria
promptly and then proceeding to persistent
colonization and an inflammatory response in
airway walls.
High prevalence in patients with CF of airway
colonization with Staphylococcus aureus,
Pseudomonas aeruginosa, and Burkholderia
cepacia, organisms that rarely infect the lungs of
other individuals

9. Clinical presentation
Most common signs/symptoms: Recurrent respiratory tract
infections
• Other signs/symptoms
o With mild disease, may be asymptomatic
o Chest
• Wheezing, chronic cough, hemoptysis, progressive respiratory
failure, cor pulmonale
• Digital clubbing
• Pansinusitis and nasal polyps
o Intestinal tract
• Meconium peritonitis, meconium ileus (10-15% of newborns
with CF), distal intestinal obstruction syndrome = meconium ileus
equivalent, intussusception, rectal prolapse.

10. Clinical presentation
o Hepatobiliary
• Cirrhosis, portal hypertension, hypersplenism, esophageal
varices that may bleed, cholelithiasis
o Pancreas
• Steatorrhea: Frequent, bulky, greasy, large, foul-smelling stools
that float in water
• 8% develop diabetes mellitus
• Occasional deficiency of vitamins A, D, E, and K
o Urogenital
• Delayed sexual development, azoospermia due to failure of
vas deferens to develop, undescended testes, hydrocele,
secondary amenorrhea
o Dry skin, salty taste to skin
o Failure to thrive

12. RADIOLOGICAL EVALUATION
 Medical imaging provides an invaluable service for the
diagnosis and treatment of cystic fibrosis.
 Each modality is valuable in detecting different symptoms
that can arise due to cystic fibrosis.
 Possible connections between abdominal and pulmonary
pathologies have increased the likelihood of catching cystic
fibrosis using multiple imaging modalities together.

13. RADIOLOGICAL EVALUATION
Prenatal diagnosis
Post natal diagnosis
Pulmonary manifestation
Extra pulmonary manifestation

14. PRE-NATAL DIAGNOSIS
 pre-natal diagnosis of CF and post-natal complications is
well documented
Fetuses with CF have been associated with hyperechogenic
fetal bowel detected by ultrasound during the second and
third trimesters of pregnancy.
 Bowel is considered hyperechogenic if its echogenicity
(brightness) is equal to or greater than that of the adjacent
iliac bone

16. Pulmonary manifestations

17. Radiography
Chest x-rays are insensitive to the early changes of cystic
fibrosis, with changes seen on HRCT in 65% of patients with
CF and normal CXR. Later changes include:
 Hyperinflation
 bronchiectasis
 lobar collapse
 pulmonary arterial enlargement due to pulmonary
arterial hypertension is seen in patients with long
standing disease

20. Brasfield scoring system
air trapping linear
markings
nodular cystic
lesions
large lesions general severity
0: absent
4: most severe
0: absent
4: most severe
0: absent
4: most severe
0: absent
3: segmental/lobar
atelectasis and
pneumonia
5: multiple
atelectasis and
pneumonia
0: absent
1-3: increasing severity
4: complications
(cardiac enlargement,
pneumothorax)
5: most severe
Is a scoring system for cystic fibrosis. It is based on plain film radiographic findings
and has been reported to have a good correlation with pulmonary function
Overall score: 25-total de merit points (the lower the overall score, the worse the
disease severity)
Minimum possible score: 3

21. HRCT chest
 HRCT has become indispensable in the monitoring of CF
patients, and is used to guide therapy and assess
response to treatment, as it not only correlates with lung
function.
 Typically scans are repeated every 6 to 18 months
depending on institution and clinical course.
 Mucous plugging is of particular importance as it is
thought to precede infective exacerbations and thus
identification of such plugging may be used to trigger
changes in therapy.
The use of low dose protocols is able to significantly reduce cumulative radiation dose

22. HRCT chest findings
bronchial wall
and / or
Peribronchial
interstitial
thickening
acute infectious
bronchiolitis
bronchiectasis mosaic
attenuation
pattern
mucus plugging
within bronchi
especially early in
the disease
• especially early
in the disease
• tree-in-bud
appearance
• centrilobular
nodular
opacities
• branching
opacities
• progresses with
time from
cylindrical to
varicose to
cystic
• signet ring sign
due to air
trapping
best seen on
expiratory scans
finger in glove
appearance

26. The nose and sinuses
 The upper airways are very frequently affected in CF, with
over 75% of patients reporting some kind of sinus or nasal
symptom such as nasal or sinus obstruction, nasal
discharge, post-nasal drip and facial pain
 Imaging findings includes small hypoplasic sinuses,
thickened nasal turbinates and thickened mucosa of the
sinuses.
 Chronic inflammation and thickening of the mucosa of
the nasal cavities and sinuses result in formation of
inflammatory polyps and the accumulation of mucus in
obstructed sinuses

28. Extra pulmonary manifestation
 Abdominal manifestations in cystic fibrosis are common,
varied and nearly all organ systems can be
affected. Only 39% of patients with cystic fibrosis (CF)
have pulmonary symptoms as their sole complaint.
This include:
 Pancreatic manifestations
 Hepatobiliary manifestations
 Gastrointestinal manifestations
 Renal manifestations
 Musculoskeletal manifestations

29. Pancreatic manifestations
 Autolysis of the pancreas due to viscous pancreatic
enzymes and obstructed pancreatic ducts is known to
start during intra-uterine life
 This leads to fibrosis, atrophy and replacement of the
pancreas by fat which clinically results in exocrine
pancreatic insufficiency and malabsorption in up to 90%
of patients.
 Pancreatic cysts are a relatively common finding in CF
and can vary in size and number. Rarely, cysts can
replace the entire pancreas in a condition called
pancreatic cystosis, which can cause pain through mass
effect

33. Hepatobiliary manifestations
Hepatobiliary manifestations are common in CF and
include fatty infiltration of the liver (steatosis), focal
biliary cirrhosis with portal hypertension,
microgallbladder and gallstones.
Patients are more frequently asymptomatic, but liver
disease is the second most common cause of death in
CF
Splenomegaly as a result of portal hypertension can
be seen as massive enlargement of the spleen causing
pain, dyspnoea and signs of hypersplenism and
sometimes complicated with splenic infarcts or
subcapsular haematomas

35. Gastrointestinal manifestations
 Meconium ileus: Bowel blockage of the newborn or
meconium ileus is seen in 15-20% of neonates with CF
and 25% of infants with meconium ileus prove to have
CF
Classically, above the obstruction the bowel is greatly
distended with fluid content, while below this level, the
distal ileum and colon are collapsed. Soon after birth,
usually in 24 to 48 hours, the newborn will present with
abdominal distension and vomiting

37. Gastrointestinal manifestations
 Distal intestinal obstructive syndrome: DIOS is the equivalent
of meconium ileus in adults.
 It affects up to 15% of CF patients as a result of thickened
intraluminal secretions, undigested food secondary to
exocrine pancreatic insufficiency and impaired bowel
motility
 Abdominal radiograph and CT show dilated small bowel
loops with fluid levels and faecal material within the small
bowel (“small bowel faeces”).

39. Gastrointestinal manifestations
 Intussusception: Intussusception is more common in CF
patients than in the general population and is seen in 1% of
paediatric patients. It is rare in adulthood and comprises 5%
of all intussusceptions and 1% of bowel obstructions
 Imaging reveals a bowel-within-bowel configuration which
is pathognomonic of the condition

41. Gastrointestinal manifestations
 Fibrosing colonopathy: has been reported in association
with children prescribed high strength pancreatic enzyme
supplements.
 Imaging has a limited role demonstrating non-specific large
bowel wall thickening and final diagnosis is usually obtained
with histology, which depicts submucosal fibrosis

42. Renal manifestation
 Nephrolithiasis: is another important differential diagnosis
of acute abdominal pain as there is a reported
increased frequency of renal stone disease in CF in
comparison to the general population.
 Initial assessment can be made with a CT of the kidneys,
ureters and
bladder (CT KUB) to confirm the diagnosis or with an
ultrasound scan if obstruction and hydronephrosis is
suspected in a patient with know nephrolithiasis

44. Musculoskeletal manifestations
Hypertrophic pulmonary osteoarthropathy
This condition consists of a triad of clubbing,
symmetric arthritis and periosteal new bone
formation
Firstly associated with brochogenic carcinoma,
it is also recognised in
bronchiectasis, chronic lung inflammation and
infection and CF

46. DIFFERENTIAL DIAGNOSIS
 Recurrent aspiration
• Often have predisposing neuromuscular abnormalities
• Bronchiectasis in lower lobes and posterior segments
i.e. the dependent portions of lungs
• Pneumonia can sometimes be related to a preceding episode of choking
or gagging with feeds
 Asthma
• Especially when complicated by ABPA and bronchiectasis
• May be seasonal
 Bronchopulmonary dysplasia
• Improves as the patient ages
• Recurrent aspiration
• History of prematurity
 Immotile cilia syndrome
• Dysfunction of cilia in respiratory and auditory epithelium
• Lower lobe predominant
• May have situs inversus
• May have associated cardiac anomalies

47. CASES

48. 24-year-old man with right-sided pleuritic chest pain
presents to the Emergency Department.

49. ▶ Chest radiograph shows increased lung volumes and diffuse interstitial opacities
emanating from the hila; many of them are parallel, indicative of bronchiectasis
(worse in the upper lungs). Branching tubular densities in the right upper lobe
represent mucus impaction in dilated bronchi. A small right pneumothorax is also
present.
▶ CT findings include bronchial wall thickening, tubular and varicoid bronchiectasis
signet-ring, mucoid-impacted bronchioles causing tree-in-bud, and mosaic

50. 26 years old male chronically ill patient
with nausea vomiting and dehydration
 Ct Images of the chest
in lung windows
demonstrated profound,
diffuse, cystic dilatation
of the airway. CT images
of upper abdomen in
soft tissue windows
demonstrate a nodular,
cirrhotic appearing liver,
splenomegaly and
complete fatty
replacement of the
pancreases