Waks PDF

Jonathan Waks, MSIII
Gillian Lieberman, MD
March 2007
Ring Enhancing Lesions in a

Patient with AIDS
Jonathan Waks, Harvard Medical School Year III

Agenda
Background: CNS complications of AIDS

Patient presentation
Menu of radiologic tests
Differential diagnosis: ring enhancing lesions
Differentiating CNS lesions
Summary

AIDS and the CNS

10% of patients have neurological signs and symptoms
when they first present with AIDS.
30-60% of patients with AIDS will develop neurological
complications during the course of their illness.
70-90% of patients with AIDS show CNS involvement at
autopsy.
Understanding and recognizing the appearance of
CNS complications in patients with AIDS is
important in promptly recognizing, diagnosing and
initiating proper treatment.
Thurnher MM. Eur Radiol 1997;7(7):1091-7

DDx. of CNS complications of AIDS:

1.
2.
HIV encephalitis
Opportunistic Infections:
3.
Toxoplasmosis
Cryptococcosis
CMV
TB
PML (JC virus)
Bacterial
Fungal
Neoplasm
HIV-1 Virus
http://www.niaid.nih.gov/factsheets/howhiv.htm
Primary CNS lymphoma

Kaposis Sarcoma
Thurnher MM. Eur Radiol 1997;7(7):1091-7

Index Patient JL
49 year old man with AIDS (last CD4=17, on
HAART) who presented to an OSH for unsteady
gait, lower extremity weakness, headache, vomiting,
dysarthria and seizures.
PE:
Temp: 102.4F
Multiple CN deficits
Head CT showed multiple ring enhancing lesions

Started on broad spectrum antibiotics with coverage
for toxoplasma.
No improvement Brain biopsy: non diagnostic
Transferred to BIDMC for further management.
5

Before we discuss the imaging that

was obtained when JL arrived at
BIDMC, lets first review the radiologic
modalities that can be used to
evaluate the CNS in a patient with
AIDS.

Menu of Radiologic Tests

Primary Modalities:
CT (w/wo contrast)
MRI (w/wo contrast)
T1, T2, FLAIR
DWI/ADC Maps
Adjunctive Modalities:
FDG-PET
Thallium 201 SPECT
Special MRI protocols
MR Spectroscopy
Perfusion MR
http://www.southernhealth.org.au/imaging/images/mr_ge.jpg


Primary Modalities:
CT (w/wo contrast)
MRI (w/wo contrast)
T1, T2, FLAIR
DWI/ADC Maps
Adjunctive Modalities:
FDG-PET
Thallium 201 SPECT
Special MRI protocols
MR Spectroscopy
Perfusion MR
These adjunctive modalities are

not used in the routine imaging or
evaluation of CNS lesions in
patients with AIDS. They are
primarily used when the identity
of a lesion is in question and
additional non-invasive imaging
would potentially alter treatment.
PET and SPECT scanning are
used most frequently. MR
spectroscopy and perfusion MR
are not routinely used and will not
be discussed in this presentation.
Adjunctive imaging modalities will be
discussed later on in the presentation
8


Computed Tomography:
Pros
Cons
1. Fast
1. Less sensitive than MRI
2. Readily available
2. Limited evaluation of
posterior fossa
3. Can scan people with

contraindications to MRI
3. Can miss some white

matter disease
4. Brain radiation
Normal Head CT
BIDMC, PACS


Magnetic Resonance Imaging:
Pros
Cons
1. Better than CT at determining if a

lesion truly is solitary
1. More costly, less readily

available
2. Increased sensitivity to subtle white

matter disease and posterior fossa
lesions
** MRI is the BEST test to

assess CNS lesions
3. May be able to identify small

peripheral lesions missed by CT that
are more accessible for biopsy
4. No radiation
5. Multiple imaging sequences can aid
diagnosis (DWI/ADC/FLAIR)
Normal T1 and T2 MRI

BIDMC, PACS
10

Diffusion Weighted Imaging (MRI)

Diffusion Weighted Imaging (DWI): Makes use of Brownian motion to
image local water diffusion. Macromolcules and cells in the brain
restrict the diffusion of water.
Areas of restricted diffusion appear BRIGHT on DWI
Apparent Diffusion Coefficient (ADC): The signal intensity of DWI

depends on factors other than diffusion information (spin density,
TR, TE). By combining multiple DWIs, these other factors can be
eliminated. ADC also eliminates T2-Shine through on DWI caused
by intense T2 signals.
Areas of restricted diffusion appear DARK in ADC

Images from Fillipi. Clinical MR Neuroimaging. pg 411
Information from Stadnik et al. http://ej.rsna.org/ej3/0095-98.fin/index.htm
11

Imaging: JL
Axial T1WI MRI
pre gadolinium
Multiple ring enhancing

Lesions throughout CNS
Axial T1WI MRI

post gadolinium
Images provided by Mizuki Nishino, MD; BIDMC
12

Looking at additional MRI sequences

allows us to better characterize the
center of the lesion and surrounding
tissue.
13

Imaging: JL
Axial
T1 MRI +Gad
Hypo/isointense lesion
with ring enhancement
Axial
DWI MRI
Hyperintense on DWI =
restricted diffusion
Images provided by Mizuki Nishino, MD; BIDMC, PACS
Axial
FLAIR MRI +Gad
Enhancing lesion
surrounded by
hyperintense edema
Axial
ADC Map
Hypointense on ADC =
14

There is a well defined differential

diagnosis for ring enhancing lesions
in the CNS:
15

DDx. Ring Enhancing Lesions (*)
Infection:
Head T1WI w/ contrast
Head CT with contrast
Toxoplasma
Cystercercosis
Brain abscess (bacterial, fungal)

Neoplasms
Brain tumors/metastases
Primary CNS Lymphoma
Demyelinating Disease
MS
ADEM
Vascular lesions
Resolving infarction
Hematoma
Thrombosed aneursm
Radiation necrosis
Postoperative changes
Gamuts in Radiology, online edition

Images from Provenzale JM, Radiol Clin North Am 1997;35(5):1127-66. 16

DDx. Ring Enhancing Lesions (*)
Infection:
Head T1WI w/ contrast
Toxoplasma
Cystercercosis
Brain abscess (bacterial, fungal)

Neoplasms
Brain tumors/metastases
Primary CNS Lymphoma
Demyelinating Disease
MS
When we consider which of these

ADEM
entities are
common in patients with
AIDSVascular
(see slide
4 for a refresher),
lesions
the differential narrows, and we can
Resolving infarction
focus on Toxoplasmosis, brain
Hematoma
abscess and
primary CNS lymphoma
Thrombosed aneursm
Radiation necrosis
Postoperative changes
Gamuts in Radiology, online edition

Images from Provenzale JM, Radiol Clin North Am 1997;35(5):1127-66. 17

We will now explore the narrowed

differential in more detail.
1. Toxoplasmosis
2. Primary CNS Lymphoma
3. Bacterial brain abscess
18

Image from http://cal.vet.upenn.edu/paraav/images/10-43.jpg
Toxoplasmosis: Background
Micrograph of T. gondii
Intracellular protazoan parasite, toxoplasma gondii

Most common opportunistic infection in HIV (CD4 < 100 per L)
Symptoms are usually secondary to reactivation of latent infection
Signs/Symptoms: headache, fever, seizures, encephalopathy,

altered mental status, neuro. deficits
Important to quickly diagnose because very treatable with antibiotics
Toxoplasma antibody is not always useful1
Only 1/3 cases have rise in IgG

Only 1/2 produce antibodies in CSF
CSF PCR lacks sensitivity and specificity1
Response to treatment is the main method of arriving at a definitive

diagnosis.
Treatment: Pyrimethamine and sulfadiazine or clindamycin
Provenzale JM, Radiol Clin North Am 1997;35(5):1127-66.
1. Fillipi. Clinical MR Neuroimaging, pg 420.
19

Toxoplasmosis: Life cycle

Cats are the main reservoirs of infection and
become infected by ingesting tissue cysts.
The cysts reproduce inside the feline
intestinal tract.
Oocysts are shed in fecal matter and are

extremely resistant to severe environmental
conditions and disinfectants.
Humans become infected by either:

Eating tissue cysts in undercooked meat
Fecal-oral transmission from cat feces
Blood or organ transplantation
Transplacentally
Approximately 22.5% of people in the United

States are infected.
Image and information from http://www.dpd.cdc.gov/dpdx/HTML/Toxoplasmosis.htm
20

Toxoplasmosis: Sites of Infection

Most common sites of
infection are:
Cortico-medullary junction
Basal ganglia
Thalamus
Image from Netter, 2004, plate 104.

21

Toxoplasmosis: Imaging
CT:
Non-contrast: isodense to gray matter, but can be detected
secondary to possible edema and mass effect
May be hyperdense if hemorrhagic
Contrast: 90% Ring-enhancement1 with is secondary to
inflammatory response (patients with decimated immune
systems may not show enhancement)2
After treatment, can show areas of calcification
1. Koralnik, UpToDate
2. Provenzale JM, Radiol Clin North Am 1997;35(5):1127-66.
22

Toxoplasmosis: Imaging
MRI:
Usually shows more lesions than CT
T1WI: hypointense or isointense to gray
matter
T2WI/FLAIR: isointense or hyperintense to
gray matter
ring enhancing, sometimes with a central
focus of enhancement target sign.
Zimmerman, RD. Clinical MR Neuroimaging. pg 365
23
Images from Thurnher MM. Eur Radiol 1997;7(7):1091-7

Toxoplasmosis Lesions
Below are 2 patients with CNS lesions that were
subsequently shown to be toxoplasmosis.
Patient 2
Patient 1
Head CT w/ contrast
Hypodense, ring
enhancing lesion and
surrounding edema
T2 MRI, non-contrast
T1 MRI w/ contrast
Hyperintense,
enhancing lesion
Hypointense, ring
enhancing lesion
24

Primary CNS Lymphoma: Background

Most common AIDS related neoplasm (2-5% patients)
After Toxoplasmosis, is second most common cerebral mass
lesion in AIDS patients.
Almost always of B-cell, Non-Hodgkins type
Likely related to EBV
Presenting symptoms: neurological deficits, encephalopathy,
seizure (similar to toxoplasmosis)
Median survival < 1 year
Treatment: Radiation and corticosteroids
25

Primary CNS Lymphoma: Sites of Infection
Most commonly located in:

periventricular/periependymal
white matter
corpus callosum
Illustrations from Netter, 2004, Plates 100, 104.

BIDMC, PACS
26

Primary CNS Lymphoma: Imaging

CT:
Isodense to Hypodense
MR:
T1: hypointense
T2/FLAIR: isointense to hyperintense
Enhancement: usually irregular enhancement
or ring enhancement.
Doweiko, UpToDate
Chang. Clinical MR Neuroimaging. pg 466
27

Primary CNS Lymphoma can have a

wide range of appearances:
28

Primary CNS Lymphoma: Varying Lesions

2 different patients with lesions subsequently shown to be primary CNS lymphoma
Patient 3
T1WI +Gad.
Hypointense lesion with
ring enhancement
Left image from Provenzale JM, Radiol Clin North Am 1997;35(5):1127-66.
Patient 4
T1WI +Gad.
Homogenously
enhancing lesion
Right Image from Doweiko, UpToDate
29

Bacterial Abscess: Background

Often presents with headache, altered mental
status, nausea, vomiting, seizures, neuro. deficits
due to expanding mass.1
Hypointense on T1, Hyperintense on T21
Capsule is hypointense on T21
Ring enhancing with surrounding edema1
Less common in AIDS patients than toxoplasmosis
or primary CNS lymphoma2
Often associated with bacteremia
1. Fillipi, Clinical MR Neuroimaging. Pg 409
2. Koralnik, UpToDate
30

Bacterial Abscess: Imaging

T1 MRI, no contrast
Hypointense lesion with

surrounding edema
T2 MRI w/ contrast
T1 MRI +Gad
Enhancing lesion with

hypointense capsule and
surrounding edema
Ring enhancing lesion with

surrounding edema
Images from Zimmerman, RD. Clinical MR Neuroimaging. pg 355
31

Lymphoma vs. Toxoplasmosis

Toxoplasmosis and primary CNS lymphoma are the two most common
brain lesions in patients with AIDS, but, as has been shown, both can
have very similar clinical features and appearance on CT and MRI.
The definitive diagnosis is usually provided by brain biopsy, but biopsy

is not a benign procedures and is associated with possible morbidity
and mortality. (8.4% morbidity, 2.9% mortality)1
Delay in diagnosis while waiting to see if a patient responds to initial

therapy is a significant problem:2
lesions can rapidly progress.
unnecessary therapies are associated with unnecessary toxicity.
Incorrect initial treatment may result in a biopsy that could have
potentially been prevented.
1. Doweiko, UpToDate
2. Fillipi, Clinical MR Neuroimaging. Pg 420
32

Lymphoma vs. Toxoplasmosis: Patient 5

The lesion has significantly
increased in size over 2 weeks
Contrast head CT of a 38 year old woman with

AIDS and a ring-enhancing lesion presumed to
be toxoplasmosis
Images from Provenzale JM, Radiol Clin North Am 1997;35(5):1127-66.
Same patients contrast head CT after 2

weeks of anti-Toxo antibiotics and no
improvement. Biopsy 2 days later
confirmed primary CNS lymphoma
33

The appearance of a CNS lesion

may give clues as to the diagnosis:
34

Lymphoma vs. Toxoplasmosis: Features

Favors Lymphoma
Favors Toxoplasma
1. Large lesion size (>4 cm)
1. Large number of lesions
2. Extensive white matter

involvement
2. Involvement of basal
ganglia
3. Periventricular location/
subependymal spread
3. Hemorrhagic lesions
4. Contrast enhancement along

ventricular surface
5. Extension across or
involvement of corpus
callosum
4. Responds to anti-Toxo
drugs, usually within 7-14
days
BUT in practice, these
features are unreliable in
making the correct diagnosis
35

Diffusion Weighted Imaging is one

specific application of MRI that has
attempted to distinguish ring-enhancing
lesions:
36

Diffusion Weighted Imaging

Can Diffusion Weighted Imaging be used to differentiate toxoplasmosis
from CNS lymphoma?
Data is inconsistent.
In general:1
* Toxoplasmosis tends to be hyperintense on DWI and hypointense on ADC
This corresponds with RESTRICTED DIFFUSION
* CNS lymphoma tends to be hypointense on DWI and hyperintense on ADC
This corresponds with INCREASED DIFFUSION
BUT, there is a broad, overlapping range of diffusion values for both lesions,
and both conditions can show either increased or restricted diffusion. As of now,
DWI/ADC cannot accurately distinguish toxoplasmosis from CNS lymphoma.
DWI/ADC is useful for identifying pyogenic abscesses which are more
consistently hyperintense on DWI and hypointense on ADC (restricted diffusion)
1. Fillipi. Clinical MR Neuroimaging pg 408-420
37

Diffusion Weighted Imaging: Examples

Patient 6:
proven Bacterial Abscess
Surrounding edema
Patient 7:
proven Toxoplasmosis
DWI
DWI
ADC
Hyperintense
Hypointense
Restricted Diffusion
Images from Zimmerman. Clinical MR Neuroimaging pg 355, 366
Lesion does NOT

show restricted
diffusion in the center
Hyperintense lesion with

Toxo. does not consistently show restricted

diffusion, even in the same patient!
38

Lymphoma vs. Toxoplasmosis

Nuclear medicine offers other methods for differentiating
between infectious and neoplastic lesions
FDG-PET scan
Image from http://upload.wikimedia.org/wikipedia/commons/c/c6/PET-image.jpg
Thallium 201 SPECT
39

FDG-Positron Emission Tomography

Patients are given trace amounts of FDG ([18F]
2-Fluoro-2-Deoxy-D-Glucose), a radioactive
form of glucose that enters and becomes trapped
in metabolically active cells. The concentration
of FDG in tissue is directly proportional to its
metabolic activity
FDG undergoes -decay
-particles collide with electrons after traveling
only a few mm. The collision produces 2
gamma rays which are detected and produce
part of an image.
http://www.biomedpet.org/howitworks.cfm
Image from http://www.scq.ubc.ca/?p=474
40

FDG-Positron Emission Tomography

FDG-PET can distinguish infectious lesions from neoplastic lesions
Toxoplasmosis/other infections:
Lymphoma:
LOW metabolic activity
HIGH metabolic activity
T1 + Gad
FDG-PET
Lesion is hypometabolic on FDG-PET

Images from Love C, Radiographics 2005;25(5):1357-68.
T1 + Gad
FDG-PET
Lesion is hypermetabolic on FDG-PET

41

Thallium 201 SPECT

PET scanning is not widely available and is more expensive than SPECT (Single Photon Emission
Computed Tomography) because the isotopes used in PET scanning have short half-lives.
201Tl
behaves like K+ and enters living cells via the Na+/K+ ATPase. It does not accumulate in
necrotic/dead tissue and thus provides another method of potentially differentiating neoplastic
from infectious lesions
201Tl
decays via the production of single photons which can be detected and imaged.
Patient 8:
T1 MRI of the brain
shows an
inhomogeneously
enhancing lesion
later shown to be
CNS lymphoma at
biopsy
Images from Antinori A, J Clin Oncol 1999;17(2):554-60.
201Tl
SPECT scan
shows a focal area
of thallium uptake
corresponding to the
neoplastic lesion
42

Patient JL -- Follow-up
Brain biopsy at OSH was not diagnostic:
Few WBC
No bacteria/organisms via Gram stain or culture
No signs of lymphoma.
Toxo antibodies negative

Toxo PCR of CSF negative
EBV PCR of CSF negative
Found to have multiple abscesses throughout
body and later found to be bacteremic
43

Patient JL -- Follow-up
Widespread bacterial infection and restricted diffusion on
DWI/ADC suggested abscess.
Restarted on broader spectrum antibiotics to cover
bacteria and toxoplasmosis.
CNS lesions began to decrease in size
Diagnosis: favored bacterial abscess, although
toxoplasmosis could not be ruled out
BIDMC, PACS
44

Patient JL: Imaging over the course of 2 months of treatment
Time
Admission
T1 MRI
w/ Gad
s/p treatment
for 1 month
T1 MRI
w/ Gad
s/p treatment
for 2 months
T1 MRI
w/ Gad
BIDMC, PACS
45

Summary
CNS complications are extremely common in patients
with AIDS.
The 2 most common CNS lesions in AIDS patients are
toxoplasmosis and primary CNS lymphoma.
Lesions are often treated empirically, but delay in
definitive diagnosis can have significant consequences.
MRI and nuclear medicine offer non-invasive methods to
facilitate the identification of CNS lesions without
invasive biopsy
46

References
1.
Antinori A, De Rossi G, Ammassari A, et al. Value of combined approach with thallium-201 single-photon emission computed tomography
and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma. J Clin Oncol
1999;17(2):554-60.
2.
Chang, Linda and Thomas Ernst. Physciological MR to evaluate HIV-associated brain disorders. Clinical MR Neuroimaging. Ed.
Jonathan Gillard et al. Cambridge: Cambridge University Press, 2005. 460-478.
3.
Doweiko JP, Groopman JE. AIDS-related lymphomas: Primary central nervous system lymphoma. UpToDate. www.uptodate.com
Accessed 3/14/07
4.
Fillipi, Christopher G. The role of diffusion-weighted imaging in intracranial infection. Clinical MR Neuroimaging. Ed. Jonathan Gillard et
al. Cambridge: Cambridge University Press, 2005. 408-428.
5.
Gamut A-61 Ring-enhancing Lesion on CT or MRI. Reeder And Felson's Gamuts In Radiology. Ed. Maurice Reeder. New
York: Springer, 2003. Accessed electronically.
6.
How does PET work? PET Imaging Center 2005. http://www.biomedpet.org/howitworks.cfm. Accessed 3/18/07.
7.
Koralnik, IJ, Approach to HIV-Infected patients with central nervous system lesions. UpToDate. www.uptodate.com Accessed 3/14/07
8.
Love, C et al. FDG PET of infection and inflammation. Radiographics. 2005; 25, 5: 1357-1367.
9.
Netter, Frank H. Atlas of Human Anatomy, 3rd Edition. Teterboro: Icon Learning Systems, 2004.
10.
Provenzale JM, Jinkins JR. Brain and spine imaging findings in AIDS patients. Radiol Clin North Am. 1997 Sep;35(5):1127-66.
11.
Stadnik, Tadeusz et al. Diffusion imaging: from basic physics to practical imaging 1998 RSNA Scientific Assembly.
http://ej.rsna.org/ej3/0095-98.fin/index.htm. Accessed on 3/16/07.
12.
Thurnher MM, Thurnher SA, Schindler E. CNS involvement in AIDS: spectrum of CT and MR findings. Eur Radiol 1997;7(7):1091-7.
13.
Toxoplasmosis. Laboratory Identification of Parasites of Public Health Concern.

http://www.dpd.cdc.gov/dpdx/HTML/Toxoplasmosis.htm. Accessed on 3/18/07.
14.
Zimmerman, Robert D. Physiological imaging in infection, inflammation and demyelination: overview. Clinical MR Neuroimaging. Ed.
47
Jonathan Gillard et al. Cambridge: Cambridge University Press, 2005. 353-379.

Acknowledgements:
Mizuki Nishino, MD
Pamela Lepkowski
Larry Barbaras, Webmaster
48

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Jonathan Waks, MSIII

Ring Enhancing Lesions in a

Jonathan Waks, MSIII

Background: CNS complications of AIDS

Jonathan Waks, MSIII

AIDS and the CNS

Thurnher MM. Eur Radiol 1997;7(7):1091-7

Jonathan Waks, MSIII

DDx. of CNS complications of AIDS:

Primary CNS lymphoma

Thurnher MM. Eur Radiol 1997;7(7):1091-7

Jonathan Waks, MSIII

Head CT showed multiple ring enhancing lesions

Jonathan Waks, MSIII

Before we discuss the imaging that

Jonathan Waks, MSIII

Menu of Radiologic Tests

Jonathan Waks, MSIII

Menu of Radiologic Tests

These adjunctive modalities are

Jonathan Waks, MSIII

Menu of Radiologic Tests

1. Less sensitive than MRI

3. Can scan people with

3. Can miss some white

Jonathan Waks, MSIII

Menu of Radiologic Tests

1. Better than CT at determining if a

1. More costly, less readily

2. Increased sensitivity to subtle white

** MRI is the BEST test to

3. May be able to identify small

Normal T1 and T2 MRI

Jonathan Waks, MSIII

Diffusion Weighted Imaging (MRI)

Areas of restricted diffusion appear BRIGHT on DWI

Apparent Diffusion Coefficient (ADC): The signal intensity of DWI

Areas of restricted diffusion appear DARK in ADC

Information from Stadnik et al. http://ej.rsna.org/ej3/0095-98.fin/index.htm

Jonathan Waks, MSIII

Multiple ring enhancing

Axial T1WI MRI

Images provided by Mizuki Nishino, MD; BIDMC

Jonathan Waks, MSIII

Looking at additional MRI sequences

Jonathan Waks, MSIII

Images provided by Mizuki Nishino, MD; BIDMC, PACS

Jonathan Waks, MSIII

There is a well defined differential

Jonathan Waks, MSIII

DDx. Ring Enhancing Lesions (*)

Head T1WI w/ contrast

Head CT with contrast

Brain abscess (bacterial, fungal)

Gamuts in Radiology, online edition

Jonathan Waks, MSIII

DDx. Ring Enhancing Lesions (*)

Head T1WI w/ contrast

Head CT with contrast

Brain abscess (bacterial, fungal)

When we consider which of these

Gamuts in Radiology, online edition

Jonathan Waks, MSIII