High b-value diffusion-weighted imaging in progressive multifocal leukoencephalopathy in HIV patients
Eur Radiol
High b-value diffusion-weighted imaging in progressive multifocal leukoencephalopathy in HIV patients
Claudia Godi 0 1 2 3 4 5
Enrico De Vita 0 1 2 3 4 5
Enrico Tombetti 0 1 2 3 4 5
Indran Davagnanam 0 1 2 3 4 5
Lewis Haddow 0 1 2 3 4 5
Hans Rolf Jäger 0 1 2 3 4 5
Hans Rolf Jäger 0 1 2 3 4 5
0 Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology , Queen Square, London , UK
1 Lysholm Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery , Queen Square, London , UK
2 Neuroradiology Department, San Raffaele Scientific Institute , Milan , Italy
3 Centre of Medical Imaging, University College Hospital , London , UK
4 Centre for Sexual Health and HIV Research, Research Department of Infection and Population Health, University College London , London , UK
5 Vita-Salute San Raffaele University , Milan , Italy
Objectives An ill-defined hyperintense edge and hypointense core on diffusion-weighted imaging (DWI) is typical of progressive multifocal leukoencephalopathy (PML). We aimed to investigate whether a b-value of 3,000 s/mm2 (b3000) can improve visualisation of PML, or provide different structural information compared to 1,000 s/mm2 (b1000). Methods We retrospectively identified HIV-positive patients with confirmed PML studied under a clinical protocol including both b1000 and b3000 DWI. The rim and core of each PML lesion and normal-appearing white matter (NAWM) were outlined on trace-weighted DWI. Signal intensities, apparent diffusion coefficient (ADC) values and volumes were measured and compared between b1000 and b3000.
Progressive multifocal leukoencephalopathy; Human immunodeficiency virus; Diffusion magnetic resonance imaging; Diffusion MRI; Diffusion-weighted MRI
-
HIV
JCV
MS
NAWM
PML
Human immunodeficiency virus
JC Virus
Multiple sclerosis
Normal-appearing white matter
Progressive multifocal leukoencephalopathy
Introduction
Progressive multifocal leukoencephalopathy (PML) is a rare,
potentially life-threatening demyelinating disease of the brain
white matter [
1
] caused by JC virus (JCV) [
2, 3
] in
immunocompromised hosts.
PML is a typical complication of patients with
HIVinfection (HIV+) [
4
], but over the last decade has been
increasingly described in the setting of
immunosuppressive regimens, including natalizumab in patients with
multiple sclerosis (MS) [
5–8
].
An early diagnosis of PML is crucial to optimise clinical
management of patients (e.g. by potentiating combined
antiretroviral therapy (cART) in HIV+ patients [
9
], or reducing
the intensity of iatrogenic immunosuppression) and to
improve long-term outcomes [
10
].
When typical pathological findings are present [
11
],
histology allows a definite diagnosis of PML. However, brain
biopsy has many drawbacks, including low sensitivity due to
sampling errors and possible complications from the invasive
procedure. Last but not least, it entails a previous clinical
suspicion of PML.
All these pitfalls highlight the importance of alternative and
less invasive diagnostic clues. Recently, the American
Academy of Neurology (AAN) Neuro-infectious Disease
Section reviewed the diagnostic criteria for PML and
established that PML diagnosis can be made with different
degrees of certainty (possible, probable and definite) upon a
combination of typical clinical imaging findings, and evidence
of JC virus in the cerebrospinal fluid (CSF) [
11
].
According to this consensus statement, imaging plays an
important role in suggesting or confirming PML diagnosis.
Compatible imaging findings are white matter lesions that
often start in the subcortical regions with involvement of the
U-fibres, and then move into the deeper white matter of the
centrum semiovale and eventually evolve into full blown,
largely confluent T2 hyperintense and T1 hypointense
nonenhancing lesions. Infratentorially the PML lesions typically
involve the middle cerebellar peduncles [
12–14
]. In the setting
of HIV infection, other conditions like HIV encephalopathy
can affect white matter and represent a diagnostic challenge
[
12, 14, 15
]. An increased MRI accuracy for PML would thus
be highly desirable in order to recognise PML lesions in case
of unspecific findings on T1- and T2-weighted images. This
may in the end reduce the necessity of brain biopsy or even of
a JCV-positive CSF for PML diagnosis.
Of note, PML lesions can show an ill-defined rim of
high signal intensity at the advancing edge and a
hypointense core on diffusion-weighted imaging (DWI)
[
16–18
]. This PML feature is peculiar and differs from
the DWI findings observed in other demyelinating and
non-demyelinating diseases [
19–21
].
Histologicalradiological comparisons demonstrated that DWI
peripheral bright rim and hypointense core were histologically
related to swollen JCV-infected oligodendrocytes at the
advancing edge of the lesion [
22, 23
] surrounding a
central area [24] of demyelinati (...truncated)