Clinical App - Dwi
Clinical App - Dwi
Clinical App - Dwi
https://doi.org/10.1007/s13244-018-0624-3
REVIEW
Received: 18 December 2017 / Revised: 12 March 2018 / Accepted: 20 March 2018 / Published online: 30 May 2018
# The Author(s) 2018
Abstract
Diffusion-weighted imaging (DWI) has revolutionised stroke imaging since its introduction in the mid-1980s, and it has also
become a pillar of current neuroimaging. Diffusion abnormalities represent alterations in the random movement of water
molecules in tissues, revealing their microarchitecture, and occur in many neurological conditions. DWI provides useful infor-
mation, increasing the sensitivity of MRI as a diagnostic tool, narrowing the differential diagnosis, providing prognostic infor-
mation, aiding in treatment planning and evaluating response to treatment. Recently, there have been several technical improve-
ments in DWI, leading to reduced acquisition time and artefacts and enabling the development of diffusion tensor imaging (DTI)
as a tool for assessing white matter. We aim to review the main clinical uses of DWI, focusing on the physiological mechanisms
that lead to diffusion abnormalities. Common pitfalls will also be addressed.
Teaching Points
• DWI includes EPI, TSE, RESOLVE or EPI combined with reduced volume excitation.
• DWI is the most sensitive sequence in stroke diagnosis and provides information about prognosis.
• DWI helps in the detection of intramural haematomas (arterial dissection).
• In diffusion imaging, ADC is inversely proportional to tumour cellularity.
• DWI and DTI derived parameters can be used as biomarkers in different pathologies.
1
Division of Diagnostic and Interventional Neuroradiology of Geneva
Echo-planar imaging (EPI) is the method of choice for clinical
University Hospitals, DISIM and Faculty of Medicine of Geneva, diffusion-weighted imaging with MRI because of its low sen-
Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14, Switzerland sitivity to the motion-induced phase errors that occur during
2
Department of Radiology, University Hospital Marqués de Valdecilla diffusion sensitisation of the MR signal. EPI is able to capture
– IDIVAL, Santander, Spain an entire image in a very short time. However, this method is
536 Insights Imaging (2018) 9:535–547
prone to artefacts because of susceptibility changes at tissue of the movement of water molecules in 3D and whether there
interfaces and has limited spatial resolution. Major technical is a dominant direction to diffusion restriction. This allows
advances in diffusion MRI have enabled superior data fidelity, tractography studies to be performed, which are multiplanar
reduced image acquisition time and an improved signal-to- reconstructions of white matter tracts according to the domi-
noise ratio (SNR) [2]. nant direction of water movement in each voxel.
Turbo-spin echo (TSE) is an adequate sequence to mini- DTI provides several quantitative parameters, most of
mise susceptibility artefacts and distortion, and it increases the which are useful in the assessment of white matter conditions.
signal-to-noise ratio. Unfortunately, it also increases acquisi- Fractional anisotropy (FA) reflects how dominant one partic-
tion times and is therefore more sensitive to motion through- ular water movement direction in a voxel is. It varies from 0 to
out the procedure. 1 and can be considered a biomarker of axonal integrity (usu-
Readout segmentation EPI techniques (e.g. RESOLVE) al- ally decreased in white matter pathologies). Mean diffusivity
low DWI and DTI to be simultaneously generated, thus reduc- (MD) represents a more exact value than ADC because it
ing the level of susceptibility-based distortion compared with considers the three main directions of water movement.
the single-shot EPI technique [3]. These also improve the over- Axial diffusivity (AD) quantifies water movement along the
all quality and spatial resolution of the images, especially when main longitudinal direction, evaluating axonal integrity, while
air-tissue interfaces are involved. However, they have longer radial diffusivity (RD) reflects myelin integrity (myelin injury
scanning times and are more sensitive to motion. Therefore, its leads to increased RD).
main clinical use is to study small regions adjacent to air-tissue As we will discuss, all these quantitative parameters im-
interfaces such as the inner ear or spinal cord [4]. prove the diagnostic possibilities of MR in the evaluation of
EPI combined with reduced volume excitation tumours, demyelinating and infectious diseases, and vascular
(ZOOMit; Siemens Healthcare, Erlangen, Germany) is a pathologies.
focused excitation method that utilises two orthogonal
pulses for slice selection in such a way that only the spins
belonging to the intersection of the slab give rise to signal. Cerebrovascular disease
This obviates the need for oversampling or distortion re-
duction [4] and allows zoomed fields of view. Advantages Stroke
of this method are improved image quality, increased im-
age sharpness and reduced distortion, with no additional Brain ischaemia leads to variations in the intra- and extracel-
acquisition time. A major disadvantage is the reduced field lular space due to a failure of the Na+/K+ ATPase and other
of view. As a result, this technique is also useful for the ionic pumps. Water movement inside the cell becomes more
evaluation of small structures, especially if they are close limited resulting in cytotoxic oedema. In addition, the intra-
to air-tissue interfaces (orbit or spinal cord). cellular environment becomes more viscous, further
Liney et al. compared EPI, RESOLVE and EPI combined restricting diffusion and decreasing the apparent diffusion co-
with reduced volume excitation, concluding that EPI provided efficient (ADC).
significantly higher ADC values than the other two sequences Subsequently, inflammatory mediation factors are released,
and that RESOLVE had the best repeatability ratio [5]. affecting the integrity of the blood-brain barrier and leading to
water extravasation and vasogenic oedema with expansion of
the interstitial space and an increase of the total water content
DWI, DTI and their derived parameters of the tissue. Subsequently, ADC values gradually increase to
their baseline. In chronic ischaemia gliosis eventually de-
Parameters derived from DWI and DTI studies allow a quan- velops, which does not result in restricted diffusion.
titative assessment, which in turn leads to improved accuracy DWI improves detection of ischaemia because it reveals al-
and reproducibility. However, it should be noted that some of terations in water diffusion before the net increase of water con-
these parameters are still subject to clinical validation [6]. tent in the subacute phase of the infarct. DWI hyperintensity [8,
ADC is the most widely used parameter derived from the 9] and changes in ADC values [10] can be found within minutes
conventional DWI sequence, representing the level of restric- from the onset of ischaemia (Fig. 1). EPI has high sensitivity and
tion to the motion of water molecules in the extracellular com- specificity in stroke diagnosis, but a negative result does not
partment. The term Bapparent^ relates to the fact that this exclude a vascular aetiology [11]. Stroke in the posterior circu-
motion is also influenced by other physiological processes, lation is more frequently DWI negative than in the anterior
such as heartbeat, breathing or CSF pulsation. The main ad- circulation (34.9% versus 15.3%, respectively; p = 0.0019) [12].
vantage of ADC relies on its widespread availability [7]. DWI is far more sensitive than conventional imaging in the
DTI is based on the application of diffusion gradients in at detection of early ischaemia. T2WI—including fluid-
least six different directions in space, enabling the evaluation attenuated inversion recovery (FLAIR) imaging—can only
Insights Imaging (2018) 9:535–547 537
detect ischaemia typically 1–4 h later, since signal abnormal- estimation of both the time of onset and the infarct-
ities on these sequences relate to the subsequent increase in salvageable brain proportion.
total water content in the infarcted area [13]. Despite some technical challenges (need for strong gradi-
In the setting of acute ischaemia, the mismatch between ents, the size of the spinal cord, flow artefacts), DWI is useful
DWI and FLAIR has been suggested to enable identification in assessing cord ischaemia. Although signal changes were
of patients with acute ischaemic stroke who are likely to be reported on both T2 and DWI in the majority of cases, DWI
within 4.5 h of symptom onset with high specificity and high showed a clear benefit over conventional MRI in some pa-
positive predictive value [14], which is useful for identifying tients, in whom T2 failed to identify an abnormality [19, 20].
candidates for fibrinolysis. According to Thurnher et al., the earliest changes on DWI in
ADC alone can be considered a biomarker of brain ischae- spinal cord ischaemia can be seen 3 h after symptom onset
mia as it allows differentiation between the two main causes of [21] An imaging protocol with DWI of the spinal cord with
increased DWI signal in acute stroke [15]: Btrue^ diffusion maximum b values between 500 and 700 s/mm2 and a slice
restriction and T2 signal elongation. ADC values also yield thickness of 3 mm is recommended [22] (Fig. 2).
timing information [16]: they start to decrease from the 1st
hour, reaching the minimal value around the 24th hour. Key points Ischaemia leads to DWI changes within minutes of
Subsequently, ADC values increase after the 3rd day, reaching symptom onset
higher values than the surrounding parenchyma after the 10th Pearls DWI helps in:
Diagnosis (most sensitive sequence)
day. When combined with T2WI signal changes, they allow
Prognosis and treatment planning (DWI aids in Bdating^
radiologists to estimate the approximate time of stroke onset. the stroke and in achieving better patient selection)
It should however be noted that haemorrhagic transformation Pitfalls False negatives for posterior circulation strokes possible
may be present, which will affect the signal of the lesion and
modify the expected sequence of events.
The area showing diffusion restriction is usually taken as
the Binfarct core^ (final infarct size), but some diffusion ab- Transient ischaemic attack (TIA)
normalities may be reversible, mainly if there is early (< 4.5 h)
spontaneous or therapeutic recanalisation of the occluded ves- The new definition of TIA is based on a biological concept
sels [17]. However, the size of the area of diffusion restriction (tissue injury). ATIA is characterised by a transient episode of
(and the ADC value) correlates with prognosis, and volume neurological impairment caused by focal ischaemia without
measurements and scores (ASPECTS, DRAGON) can be use- acute infarction [23].
ful tools in predicting the outcome after intravenous throm- Previously, TIA was defined based on arbitrary timing (du-
bolysis [18]. ration ≤ 24 h). However, permanent tissue damage (infarction)
Thrombolytic or endovascular therapies are the treatment is possible even when focal transient neurological symptoms
options for acute stroke. Selection of patients eligible for these last < 1 h [24]. Additionally, approximately 50% of patients
therapies is critical to achieve good outcomes and avoid fatal with classically defined TIA syndromes have corresponding
complications. Both time from stroke symptom onset to treat- ischaemic lesions on brain MRI diffusion- or perfusion-
ment and the individual therapeutic time window secondary to weighted imaging. Therefore, whether a symptomatic ischae-
variations in collateral circulation determine the long-term mic episode will result in ischaemic infarction cannot be based
functional outcome after stroke. Therefore, imaging—includ- solely on time duration.
ing DWI—has great prognostic value and is crucial to treat- The current definition takes imaging into account as DWI
ment decision making because it allows early diagnosis and an must be normal for the diagnosis of TIA to be upheld. If MRI
538 Insights Imaging (2018) 9:535–547
shows areas of restricted diffusion in a patient whose symp- useful in the diagnosis of acute dissection, when the intramural
toms have resolved and lasted less than 24 h, the term cerebral haematoma can barely be detected on fat-saturated T1-weight-
infarction with transient symptoms is preferred [25]. Once a ed images because of obscuration of its isointense signal by the
morphological change has been demonstrated on imaging, the surrounding soft tissues with similar signal intensity.
risk of full-blown stroke is higher, and treatment should be DWI using EPI usually shows susceptibility artefacts at the
more aggressive. air-tissue or bone-soft tissue interfaces. Artefacts present as a
fuzzy linear hyperintensity or diffuse hypointensity, which are
usually easy to differentiate from the focal round or linear
Key points New definition that takes imaging into account (DWI -) well-demarcated hyperintensity typical of intramural
Pearls If DWI +, the term cerebral infarction with transient haematoma [28]. Correlation with T1- or T2-weighted images
symptoms is preferred (more aggressive treatment)
is also helpful. The use of an SE sequence, reducing the echo
Pitfalls The duration of ischaemic symptoms does not predict
whether a symptomatic ischaemic event will result in
time and increasing the acquisition matrix, may be helpful to
ischaemic infarction minimise these susceptibility artefacts.
Tumours
DTI and tractography reconstruction can be helpful for potentially interpreted as residual tumour or tumour progres-
surgical planning in patients with brain or spinal cord masses. sion (Fig. 7).
It shows white matter tracts as well as displacement or inter- Regarding paediatric tumours, DWI can non-invasively
ruption of these tracts secondary to different pathologies. add valuable information that can be used to narrow the dif-
Slow-growing tumours displace the fibres surrounding the ferential diagnosis of the three most common tumours of the
lesion, whereas in ischaemia or trauma, representing more posterior fossa in children (medulloblastoma, ependymoma,
acute insults, the fibres are usually interrupted [45] (Fig. 6). pilocytic astrocytoma). Several studies have demonstrated that
An additional important use of DWI after surgical resection ADC values in the enhancing, non-necrotic, non-oedematous,
of a tumour is to detect areas of diffusion restriction in the solid parts of cerebellar tumours are negatively correlated with
cavity margins on MRI performed in the first 48 h, corre- tumour grade [46] (high-grade tumours such as medulloblas-
sponding to small postsurgical infarctions. The importance toma are characterised by high cellularity, low extracellular
of this imaging time window lies in the fact that the majority space, and cells with large nuclei and high nuclear-to-
of these infarcts will enhance after 1 or 2 weeks and could be cytoplasmatic ratios, causing decreased diffusion). Cutoff
values of > 1.4 × 103 mm2/s for juvenile pilocytic astrocytoma
and < 0.9 × 103 mm2/s for medulloblastoma have been sug-
gested with a high specificity [47]. An even greater accuracy
can be achieved by combining DWI and MRS to obtain more
information about the tumour proliferative potential [48].
DWI has also been reported to be useful in detecting relapse
of embryonal tumours such as medulloblastoma, being more
sensitive than contrast-enhanced MRI in subjects with the
classic variant [49].
Infection
Fig. 5 Primary CNS lymphoma. Left frontal periventricular lesion
showing prominent diffusion restriction, presenting with hyperintensity
on DWI (a), low ADC value (b) and mild hyperintensity on T2WI (c), all
Abscesses of the brain can be bacterial, parasitic or fungal in
typical features of this type of hypercellular tumour. T1WI post origin. The appearance of bacterial abscesses on conventional
gadolinium (d) shows homogeneous and intense contrast enhancement imaging varies with the stage of abscess formation, but the
Insights Imaging (2018) 9:535–547 541
typical features of the early capsule stage (ring-enhancing Aspergillus CNS infections tend to be haemorrhagic,
lesion with a T2 hypointense rim and variable degree of which is an additional cause of restricted diffusion. In general,
associated vasogenic oedema) can be similar to primary cystic it is important to include fungal abscesses in the differential
or necrotic tumours (Fig. 8) and subacute haematomas
(Fig. 9). However, pyogenic abscesses show restricted diffu-
sion with markedly decreased signal on the ADC map and
elevated fractional anisotropy (FA) within the abscess cavity
[50] because of the presence of intact inflammatory cells and
bacteria. These impede the microscopic motion of water mol-
ecules, which helps to narrow the differential diagnosis of
ring-enhancing lesions (exceptions exist: metastases with high
cellularity and haemorrhagic metastasis).
Reddi et al. showed that diffusion-weighted imaging had a
sensitivity and specificity of 96% for the differentiation of brain
abscesses from primary or metastatic cancers (positive predic-
tive value, 98%; negative predictive value, 92%) [51] (Fig. 10).
A study [52] has shown that the abscess cavity had lower ADC
and higher FA compared with the cystic cavity of glioblastomas
and metastases, possibly representing high viscosity and
organised viable inflammatory cells. In addition, FA values were
higher in the enhancing rim of the abscess than in glioblastoma
and metastasis, maybe because of the presence of concentric
layers of collagen fibres. Regarding the peritumoral zone of
oedema, this study showed that the presence of a hyperintense
FA rim (with lower FA values) was much more frequent in
glioblastomas and metastases than in abscesses. This suggests
that microstructural changes in the oedematous white matter
immediately surrounding the abscess may be different from
those surrounding glioblastoma and metastasis, possibly be-
cause of acute versus longer time to formation, respectively.
Fig. 7 Post-surgical ischaemia. Immediate follow-up MRI in a patient
Fungal abscesses can have either restricted or elevated dif- who underwent surgery for resection of a suspicious enhancing mass. In
fusion in the centre (depending on the content), in opposition the medial aspect of the resection cavity (asterisk) there is an enhancing
to pyogenic and tuberculous abscesses that typically show area on the T1 post-contrast sequence (c, arrow). This finding alone could
restricted diffusion in the core of the cavity [53]. Restricted represent residual tumour, but the presence of restricted diffusion with
high signal on DWI (a) and a low ADC value (b) meant that a small area
diffusion is usually demonstrated in the projections and wall of peri-surgical ischaemia was more likely. Three-month follow-up T1
of the fungal abscess, referred to as Bintracavitary projec- post-gadolinium MRI (d) shows absence of enhancement in the same
tions^, and represent the fungal organism itself. region (arrowhead), confirming this diagnosis
542 Insights Imaging (2018) 9:535–547
diagnosis in immunocompromised patients because of differ- and allows distinction of two parts in the lesions: a central core
ent targeted antifungal treatment. (whose size can correlate to the clinical status and disease
Parasitic abscesses may also show both restricted and ele- duration) and a peripheral rim (which includes a heteroge-
vated diffusion [54]. For example, cysticercosis cysts have a neous component and areas of surrounding cytotoxic oedema
similar or slightly increased DWI signal to CSF, and the sco- with low ADC and areas of vasogenic oedema and glial repair
lex may be seen as a hyperintense focus inside [55]. In toxo- with intermediate ADC) [64].
plasmosis, diffusion restriction is highly variable (possibly
overlapping with lymphoma characteristics, its main differen- Key points Inflammatory cells and bacteria within an abscess core
tial diagnosis) [56, 57]. In cerebral malaria, DWI is useful in restrict diffusion
detecting areas of brain infarction [58]. Pearls ADC values and morphology within the area showing
restricted diffusion may help in differentiating abscess
In the postsurgical setting, the accuracy of DWI in the diag-
from tumour and pyogenic from fungal abscess
nosis of CNS infectious complications is low, showing a high The location of diffusion restriction may orientate in the
false-negative rate. There are often postoperative changes with aetiology of viral encephalitis: limbic system for herpes
diffusion restriction due to haemorrhage/ischaemia, which can simplex; splenium of the corpus callosum for influenza
and Epstein-Barr viruses; thalami for West Nile virus
hinder the distinction between purulent content and
DWI most sensitive technique in the early stages of CJD
haemorrhagic/ischaemic components. The absence of restricted
Pitfalls Subacute haematoma can look like an abscess
diffusion is not sufficient to exclude the presence of pyogenic
postcraniotomy infection and should not be used as the main
determinant in patient management in this clinical setting [59].
Diffusion restriction is commonly seen in viral encephali-
tis, and the location of the affected area may guide the radiol- Creutzfeldt-Jakob disease
ogist in the identification of the infectious agent. For example,
the limbic system (medial temporal and inferior frontal cortex) Creutzfeldt-Jakob disease (CJD) is the combination of pro-
is the typical involved area in herpes simplex encephalitis. gressive dementia and pyramidal, extrapyramidal, and/or cer-
Viruses more frequently causing potentially reversible lesions ebellar signs caused by a prion (proteinaceous particle without
in the splenium of the corpus callosum are the influenza virus DNA or RNA but capable of causing infection). DWI MR has
[60], Epstein-Barr virus, HHV-6 and papovirus JC [61]. high diagnostic accuracy and is the most sensitive neuroimag-
Thalamic involvement is typically seen with the West Nile ing technique for striatal and cortical lesions from an early
virus [62], Japanese encephalitis or Eastern equine encephali- stage [65]. Typically, diffusion-weighted hyperintensity is
tis. DWI may help detect lesions earlier than conventional MR progressive and persistent over many weeks, affecting the
imaging. In patients diagnosed with West Nile virus encepha- striatum and cortex. The gyriform DWI-hyperintense areas
litis, diffusion restriction with no FLAIR or T2 signal abnor- in the cerebral cortex (Bcortical ribbon^ sign) correlate to the
malities has been reported to be a sign of good prognosis [63]. location of periodic sharp-wave complexes on EEG [66].
Progressive multifocal leukoencephalopathy (PML) is sec- DWI hyperintensity may resolve late in the disease.
ondary to the infection of oligodendrocytes by the JC polyoma The pulvinar sign (symmetrical hyperintensity in the pos-
virus, which typically remains latent until reactivation in the terior thalamic nuclei on DWI or T2WI), Bhockey stick^ sign
context of an immunocompromised state (HIV, natalizumab (signal changes affecting the dorsomedial thalamic nuclei) or
or other immunosuppressive treatments). Due to its ability to similar changes in the periaqueductal grey matter were report-
investigate white matter architecture and diseases, DWI shows ed to be specific for variant (vCJD) [67], but can also occur,
regions of active infection and cell swelling with high signal although less frequently, in sporadic (sCJD).
Insights Imaging (2018) 9:535–547 543
Fig. 9 Subacute haematoma. Right parietal mass (arrowhead) showing differentiate haemorrhage from abscess. There is also a subacute ischae-
diffusion restriction within the core on DWI and ADC maps (a and b, mic lesion in the inferior right frontal lobe (arrows) that shows early
respectively) and a ring-enhancing pattern on T1 post gadolinium (c). pseudonormalisation of the ADC and gyriform enhancement post
This was a subacute haematoma. Clinical context is important to gadolinium
Neuritis
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78. Purohit BS, Vargas MI, Ailianou A et al (2016) Orbital tumours and
tumour-like lesions: exploring the armamentarium of Springer Nature remains neutral with regard to jurisdictional claims in
multiparametric imaging. Insights Imaging 7(1):43–68 published maps and institutional affiliations.