CME Topic

Diffusion-Weighted Imaging: Not All That
Glitters Is Gold
Archit Bhatt, MD, MPH, Amit Masih, MD, Heather F. Grothous, BA,
Muhammad U. Farooq, MD, Bharath Naravetla, MD, and Mounzer Y. Kassab, MD, MA
Abstract: Diffusion-weighted imaging (DWI) is a sophisticated
magnetic resonance imaging (MRI) technique with rapid acquisition
time and high sensitivity for depicting acute cerebral ischemia. It is
currently part of the routine workup in most medical centers when
ischemic stroke is in the differential diagnosis. DWI helps establish
a diagnosis of acute ischemic infarct even in cases where the clinical
presentation is not typical for ischemic stroke. However, contrary to
popular belief, not every hyperintensity on DWI is an ischemic
stroke. Consequently, DWI with high intensity signals, commonly
called “positive” DWI, is sometimes misinterpreted and leads to
incorrect medical management. In this report, we briefly discuss
some of the essential, technical aspects of DWI and report various
clinical scenarios, which may lead to “positive” DWI findings but
are not ischemic strokes. Although the sensitivity of DWI for ischemic stroke is very high, the specificity is not as high, and a “positive” DWI does not exclude other diagnoses that should be considered based on each patient’s clinical history and examination, and
the appearance of other sequences of MRI scans.
Key Words: diffusion-weighted imaging, magnetic resonance imaging, stroke

M

agnetic resonance imaging (MRI) is a diagnostic technique that utilizes a magnetic field to align the hydrogen (H) atoms in the studied tissue.1 H nuclei, or protons,
have magnetic properties that allow them to spin on an axis,
known as nuclear spin, and uniformly align once placed in a
large, external magnetic field. After the initial alignment has
occurred within the main field, a second external magnetic
field is applied at a different radiofrequency and placed perpendicular to the original magnetic field. This disrupts the
initial alignment, letting the protons drift back, realign, and

emit a radiofrequency signal that is captured by the MRI
scanner. The rate of this realignment varies with the composition and type of the tissues in the body. This results in a
production of a differential, tissue-specific signal on the final
MRI acquisition image. Diffusion-weighted imaging (DWI)
is a sensitive technique that detects the mobility of water
molecules in the brain parenchymal tissue.1–3 By their distinctive inherent virtue, water molecules are always in random motion, which is constant in a given isotropic medium.
This theory is termed the Brownian motion of water molecules. The human brain tissue is an anisotropic heterogenous
environment. Movement of water molecules across the cell
membranes, blood vessels, and axons is tissue specific due to
the variability in type, density, and chemical composition of
the tissues. Diffusion-weighted imaging is thus an extension
of the original MRI technique that is achieved by combining
it with two diffusion gradient pulses. This allows monitoring
of the displacement of water molecules, which can be classified into three categories: free diffusion, restricted isotropic
diffusion, and restricted anisotropic diffusion. Free diffusion
is seen when water is displaced freely in multiple directions,
such as that found in the cerebral spinal fluid.1–3 Restricted
isotropic diffusion is found when water molecules are re-

From the Department of Neurology and Ophthalmology and Division of
Cerebrovascular Disorders, Michigan State University, East Lansing, MI.
Reprint requests to Mounzer Y. Kassab, MD, MA, A-217, 138 Service Road, Clinical Center, East Lansing, MI 48824. Email: mounzer.kassab@ht.msu.edu
None of the authors have any conflicts of interest to report or financial
disclosures to declare.
Accepted January 15, 2009.
Copyright © 2009 by The Southern Medical Association
0038-4348/0⫺2000/10200-0923

Southern Medical Journal • Volume 102, Number 9, September 2009

Key Points
• Diffusion-weighted imaging is a widely used MRI
technique with rapid acquisition time.
• A hyperintense signal on DWI is very sensitive to
detect acute cerebral ischemia but is not specific, ie
not every hyperintensity on DWI is an ischemic stroke.
• The most common cause of hyperintense lesions on
DWI, commonly referred to as positive DWI, are ischemic strokes.
• Non-ischemic lesions that appear very bright on T2
weighted images, commonly referred to as T2 shine
through, can cause a hyperintense signal on DWI.
• Apparent diffusion coefficient (ADC) mapping plays
a critical role in reaching the final diagnosis; a low
intensity signal on the ADC map and a high intensity
signal on DWI mostly signify an ischemic infarct.

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Bhatt et al • Diffusion-Weighted Imaging

stricted in motion in a certain spatial direction, which is what
occurs in the case of an abscess. Restricted anisotropic diffusion occurs when a structural lesion allows and directs the
water molecule displacement.
To obtain DWI, a pair of strong gradient pulses is added to
the pulse sequence. The diffusion data can then be presented as
signal intensity or as an image map of the apparent diffusion
coefficient (ADC). Calculating the ADC requires two or more
acquisitions with different diffusion weightings. A low ADC
corresponds to a high signal intensity (restricted diffusion) and a
high ADC to low signal intensity on diffusion-weighted images.1–3
In the setting of acute cerebral ischemia, if the cerebral
blood flow is lowered to 10 mL/100 gm/min, sodium ion
pump failure leads to excessive sodium in the cell, which is
followed by a net movement of water from the extracellular
to intracellular compartment and cytotoxic edema. Diffusion
of the water molecules in the intracellular compartment is
restricted by the cell membranes. The restricted diffusion
results in a decreased ADC and increased signal intensity
(hyperintensity) on DWI.

Case Reports
Patient 1
A 60-year-old healthy man came to the emergency
department after a generalized tonic clonic seizure with
focal onset at home manifesting by motor activity of
the right arm and leg. The seizure was associated with
postictal weakness of the right arm and right leg, confusion, and bladder incontinence. Additional history
taken in the emergency department revealed that the
patient was having daily morning headaches for the
last 4 weeks.
On the initial clinical evaluation, the patient was
drowsy, his gaze had no preference, and both pupils were
equally reactive to light. There was a mild weakness of
the right arm and leg.The plantar response was extensor
on the right. The rest of the neurological and physical
examination was unremarkable. Initial laboratory examination was normal. A computed tomography (CT) scan of
the brain showed left frontoparietal hypodensity suggesting
an ischemic stroke in the differential diagnosis. The patient
was started and maintained on phenytoin thereafter.
Over the next 12 hours, the patient’s clinical status
improved back to baseline. MRI of the brain (Fig. 1,
Patient 1) revealed a heterogeneously contrast enhanced
mass in the left frontoparietal region suggestive of a
possible primary malignant glioma. The DWI showed a
bright “hyperintense” signal in the same region (see
image of Patient 1 in Fig. 1). Excisional biopsy confirmed the diagnosis of a glioblastoma multiforme.

924

Patient 2
A 55-year-old man in his usual state of health until
two weeks prior to admission started to have left hemicranial headaches that were not relieved by traditional
medications. He had a history of essential hypertension
and was not taking anticoagulants or antiplatelets. He
denied taking any illicit drugs, over-the-counter medications, or herbal remedies. On the day of admission, a
brain CT scan showed left parietal lobe hemorrhage.
Initial clinical evaluation revealed normal mental status, and speech and language evaluation revealed rightleft confusion, agraphia, and acalculia. The rest of the
neurological examination was normal. His blood pressure was 140/90 mm Hg in the emergency room and the
basic laboratory examination, including coagulation profile, complete blood count, and comprehensive metabolic
profile, were normal. The patient’s urine toxicological
profile was normal. The brain MRI scan (Fig. 1, Patient
2) showed intraparenchymal hemorrhage in the left parietal region with hyperintensity on DWI.

Patient 3
A 64-year-old, right-handed man had a past medical
history of left temporal ischemic stroke and mild residual
right hemiparesis (National Institute of Health Stroke
Scale [NIHSS] of 2). Two years after being clinically
stable, he presented to the emergency room with an acute
complaint of slurred speech, expressive aphasia, and a
worsening of his right-sided weakness. The initial evaluation by the stroke team revealed an NIHSS of 12.
There was no evidence of any abnormal involuntary
movement and a new stroke was in the differential diagnosis. He was immediately taken to have a CT scan of
the brain, computed tomography angiogram (CTA), and
brain computed tomography perfusion (CTP) as part of
the acute stroke work-up protocol. The CTA did not
show any hemodynamic significant stenosis and the CTP
revealed evidence of hyperperfusion around the area of
his previous infarct in the left temporal lobe. His electroencephalography (EEG) revealed epileptiform discharges over the left temporal region. His brain MRI
revealed encephalomalacia in the left temporal lobe. The
left hippocampus was edematous and hyperintense on
T2-weighted image (T2-WI), fluid-attenuated inversion
recovery (FLAIR), and DWI (Fig. 1, Patient 3).
Intravenous (IV) lorazepam and levetiracetam
1000 mg were given and the patient was maintained
on oral levetiracetam 500 mg twice daily. The patient’s symptoms quickly improved, and he was discharged the next day. Five weeks later, the diffusionweighted findings disappeared on a repeat brain MRI.
(continued next page)

© 2009 Southern Medical Association

CME Topic

Neurologically, there was evidence of left upper
motor neuron facial nerve palsy and mild left-sided
weakness. MRI of the brain (Fig. 2, Patient 6) revealed a DWI hyperintense lesion in the right frontal
lobe. An incisional biopsy of the lesion showed evidence of pus, which was drained and cultured. Staphylococcus aureus was isolated from the cultures. The
patient did well after one month of intravenous
vancomycin.

(Case Report continued from previous page)

Patient 4
A 22-year-old woman with a history of left optic
neuritis four years prior to admission came in with left
face, arm, and leg numbness for three days. The numbness was patchy and not associated with any weakness or
clumsiness.
On clinical examination, there was decreased light
touch and temperature sensation on the left face, arm,
and leg. There was no evidence of weakness, ataxia, or
cranial nerve deficits. Vision was 20/20 in both eyes with
intact color vision. Fundus examination showed no abnormalities in the optic nerve. There was no impairment
of the extraocular movements. Her brain MRI (Fig. 2,
Patient 4) showed a hyperintense cerebral lesion on DWI.
The initial laboratory examination was normal including:
erythrocyte sedimentation rate (ESR), lupus antibody,
complete blood count, comprehensive metabolic panel,
coagulation profile, serum vitamin B12 level, and rapid
plasma reagin. Her cerebral spinal fluid (CSF) examination showed no evidence of infection, but revealed “eight”
oligoclonal bands. A diagnosis of multiple sclerosis was
made and the patient was started on disease modifying
therapy.

Patient 5
A 59-year-old man with a history of hypertension
and dyslipidemia came with right-sided weakness for
eight hours prior to admission. He had a significant
family history of cardiac disease. The initial clinical
examination revealed normal mental status, speech,
and cranial nerve examination. There was mild weakness of his right upper and lower extremities. His reflexes were symmetric, except for an extensor plantar
response on the right. There was no ataxia. Laboratory
exam showed normal complete blood count, comprehensive metabolic panel, electrocardiogram (EKG),
cardiac enzymes, and coagulation profile. A CT scan
of the brain was normal and the MRI of the brain (Fig.
2, Patient 5) showed left frontal lobe hyperintensity in
diffusion-weighted imaging and corresponding hypointensity on ADC. T2 FLAIR images were hyperintense in the corresponding region.

Patient 6
A 42-year-old man with a history of recent tooth
extraction for a molar tooth abscess came to the hospital
with a 2-day history of left-sided weakness. Relevant
medication and medical history were unremarkable. On
clinical examination he was febrile with a temperature of
101.4° F, but the rest of his vital signs were normal.

Discussion
The most common cause of hyperintense lesions on DWI,
commonly referred to as “positive” DWI, is ischemic stroke.
MRI-DWI has been shown to be superior to conventional
T2-WI in detecting acute ischemic stroke, whereas both techniques assist in determining the age of ischemia.4
In patients who present with symptoms of ischemic
stroke, diffusion-weighted images are very helpful in identifying any area of acute ischemia and discriminating between new and old infarction, as well as other acute and
chronic lesions in the brain. Only the acute infarcts appear
hyperintense on the diffusion. Ischemic strokes on some
occasions can be isointense on DWI. This is especially true
when the MRI scan is obtained very early after the onset
of symptoms or in some cases of small ischemic insults to
the posterior circulation territory or other very small lacunar infarcts.5 Just as a normal “negative” DWI does not
always rule out the small possibility of ischemic stroke, a
hyperintense (positive) lesion on DWI does not always
mean ischemic stroke. The Table enlists the variety of
disorders that have the potential to cause hyperintense signals on DWI.
Nonischemic lesions that appear very bright on T2-WI
can cause hyperintense signals on DWI, also known as a
T2-weighted shine through. This is the second most common cause of a hyperintense signal on DWI (after ischemic
stroke). In these cases, ADC mapping plays a critical role
in reaching the final diagnosis and only true restriction in
diffusion, as seen in the case of ischemic stroke, gives a
decreased signal on ADC. Therefore, in the overwhelming
majority of cases, a low intensity signal on ADC mapping
and a high intensity signal on DWI mostly signifies an
ischemic infarct.4,6
Intracranial abscesses and metastasis7 may also exhibit
restricted diffusion due to the presence of thick cellular necrotic debris, especially in the core of the lesion. The diagnosis in these cases is usually based on the signal differences
observed on T1 and T2-weighted sequences and the presence
or absence of contrast enhancements seen on T1-weighted
images. For example, the MRI scan of patient 6 showed a low
signal on ADC and a high signal on diffusion, a pattern
similar to the one seen in ischemic stroke. However, there

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Fig. 1 Patient 1: Hyperintensity in the left frontoparietal region on diffusion-weighted imaging (DWI). Apparent diffusion
coefficient map shows hyperintensity in the corresponding region. Corresponding regions on FLAIR imaging show hyperintensity with vasogenic edema in the surrounding areas. T1 with contrast sequence shows heterogenous contrast enhancement.
Findings are suggestive of a primary malignant brain tumor, most likely malignant glioma. Patient 2: DWI shows hyperintensity
in the left parietal region with corresponding hypointensity on ADC mapping. FLAIR imaging shows a rim of hyperintensity
and subtle hypointensity in the center. T1 with contrast imaging shows hyperintensity with peripheral contrast enhancement.
There is presence of peripheral hyperintensity in FLAIR images consistent with edema. These findings are consistent with late
subacute hemorrhage. Patient 3: First diffusion DWI reveals a hyperintensity in the left temporal lobe. Repeat DWI after 5
weeks reveals the resolution of the hyperintensity. Corresponding FLAIR and ADC images were isointense on both instances.
T1 with contrast images are unremarkable. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; ADC,
apparent diffusion coefficient.

was evidence of vasogenic edema and contrast ring enhancement that are not typically seen in acute ischemic strokes,
which is readily observed on T2 [FLAIR] and T1 after contrast images. Similarly, a late subacute bleed (Patient 2) can
clinically and radiographically (hyperintense DWI) mimic an
ischemic stroke. However, a hyperintense signal on T1-WI,
which is seen with subacute intracranial hemorrhage, is not
seen with ischemic stroke.8 Additionally, other intracranial
lesions, such as gliomas (Patient 1, Fig. 1) can show restricted

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water diffusion that indicates high cellularity, which is highly
indicative of a high-grade glioma.9
Current evidence suggests that DWI is also sensitive
to detect demyelination in cases of multiple sclerosis. Multiple sclerosis plaques (which are primarily hyperintense
on T2-weighted lesions) are caused by a breach of the
normal tissue integrity and structure. This breach affects
the diffusion of water molecules across the brain tissue
resulting in a restricted diffusion signal. The ADC signal
© 2009 Southern Medical Association

CME Topic

Fig. 2 Patient 4: Hyperintense lesion on DWI and T2/FLAIR in right thalamus and internal capsule region. There is corresponding
hypointensity with a rim of hyperintensity on apparent diffusion coefficient (ADC) maps. Additionally, there are T2 hyperintense
lesions in the subcortical periventricular regions. T1 with contrast images are negative. Patient 5: DWI shows left frontal lobe
hyperintensity and corresponding hypointensity on ADC. T2 FLAIR images show hyperintensity in the corresponding regions. These
findings are consistent with an acute ischemic stroke. Patient 6. DWI shows hyperintense lesion in the right frontal lobe with
corresponding hypointensity on ADC. There is evidence of edema as seen on ADC and FLAIR images which surround the lesion.
Contrast enhancement shows ring enhancement. DWI, diffusion weighted imaging; FLAIR, fluid-attenuated inversion recovery; ADC,
apparent diffusion coefficient.

for multiple sclerosis lesions is usually hyperintense but
can be isointense or hypointense. It has also been shown
that a mean lesion ADC of secondary progressive multiple
sclerosis was significantly higher than relapsing and remitting multiple sclerosis.10,11
Finally, an ictal, early postictal, or interictal state (Patient
3) can cause hyperintense lesions on DWI.12 As previously
described,12 increased signal on DWI, with corresponding
low or normal ADC, may be present in seizure patients. However, unlike stroke, the abnormalities in this case are reversible and do not follow a typical vascular distribution. The
abnormalities are presumed to be due to transient cortical

irritability related to hypoperfusion in the epileptic zone13 or
transient vasogenic edema due to the breakdown of the bloodbrain barrier.14

Conclusion
Our report emphasizes that despite DWI’s high sensitivity in confirming ischemic stroke, not all hyperintense
diffusion lesions are ischemic strokes. DWI’s specificity
for ischemic stroke is dependent on a given clinical scenario and interpretation of other imaging modalities of
MRI (ADC, T2, T1, and FLAIR). Awareness and knowl-

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Bhatt et al • Diffusion-Weighted Imaging

Table. Lesions that can be bright on diffusion-weighted
imaging
Acute and subacute ischemic infarct
Venous infarcts
Brain abscess
Brain metastasis
Acute demyelination (like multiple sclerosis plaques)
Tumor undergoing central necrosis
Tumor with high nuclear cytoplasmic ratio
Acute encephalitis (as in herpes simplex encephalitis)
Subacute hemorrhage
Bright lesions on T2-weighted imaging (shine-through phenomenon)
Seizure

edge of this imaging technique helps to enrich diagnostic
skills and provides better insight to the correlation between
clinical and radiological perspective of the disease, which
eventually leads to the proper management.

4. Lutsep HL, Albers GW, DeCrespigny A, et al. Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke. Ann Neurol 1997;41:574 –580.
5. Sylaja PN, Coutts SB, Krol A, et al. When to expect negative diffusionweighted images in stroke and transient ischemic attack. Stroke 2008;
39:1898 –1900.
6. Culebras A, Kase CS, Masdeu JC, et al. Practice guidelines for the use of
imaging in transient ischemic attacks and acute stroke. A report of the
Stroke Council, American Heart Association. Stroke 1997;28:1480 –1497.
7. Hartmann M, Jansen O, Heiland S, et al. Restricted diffusion within ring
enhancement is not pathognomonic for brain abscess. AJNR Am J Neuroradiol 2001;22:1738 –1742.
8. Fischbein NJ, Roberts TP, Dillon WP. Bleed or stroke? Diffusion measurements in intracranial hematomas. AJNR Am J Neuroradiol 2000;21:
1179 –1180.
9. Baehring JM, Bi WL, Bannykh S, et al. Diffusion MRI in the early
diagnosis of malignant glioma. J Neurooncol 2007;82:221–225.
10. Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology 2005;65:1526 –1532.
11. Filippi M, Inglese M. Overview of diffusion-weighted magnetic resonance studies in multiple sclerosis. J Neurol Sci 2001;186(suppl 1):S37–
S43.
12. Lansberg MG, O’Brien MW, Norbash AM, et al. MRI abnormalities
associated with partial status epilepticus. Neurology 1999;52:1021–1027.

References
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3. Le Bihan D, Breton E, Lallemand D, et al. MR imaging of intravoxel
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13. Mathews MS, Smith WS, Wintermark M, et al. Local cortical hypoperfusion imaged with CT perfusion during postictal Todd’s paresis. Neuroradiology 2008;50:397– 401.
14. Hong KS, Cho YJ, Lee SJ, et al. Diffusion changes suggesting predominant vasogenic oedema during partial status epilepticus. Seizure
2004;13:317–321.

Please see Dr. Mughis Sheerani’s editorial on
page 880 of this issue.

“Technology is a way of organizing the universe so that
man doesn’t have to experience it.”
—Max Frisch

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© 2009 Southern Medical Association