Improving the Recognition and Management of Amyloid-Related Imaging Abnormalities (ARIA) in Alzheimer’s Disease Treatment: Practical Tools & Strategies for Radiology & Neuroradiology Specialists
Co-Chairs, Jerome A. Barakos, MD, and Tammie L.S. Benzinger, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer's disease for this CME/AAPA activity titled “Improving the Recognition and Management of Amyloid-Related Imaging Abnormalities (ARIA) in Alzheimer’s Disease Treatment: Practical Tools & Strategies for Radiology & Neuroradiology Specialists.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/48NS10t. CME/AAPA credit will be available until March 14, 2025.
Similaire à Improving the Recognition and Management of Amyloid-Related Imaging Abnormalities (ARIA) in Alzheimer’s Disease Treatment: Practical Tools & Strategies for Radiology & Neuroradiology Specialists
Similaire à Improving the Recognition and Management of Amyloid-Related Imaging Abnormalities (ARIA) in Alzheimer’s Disease Treatment: Practical Tools & Strategies for Radiology & Neuroradiology Specialists (20)
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Improving the Recognition and Management of Amyloid-Related Imaging Abnormalities (ARIA) in Alzheimer’s Disease Treatment: Practical Tools & Strategies for Radiology & Neuroradiology Specialists
1. Appropriate Use of Anti-Aβ Monoclonal Antibodies in
Clinical Practice: Baseline Radiographic Exclusion Criteria1,2
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
1. Cummings J et al. J Prev Alzheimers Dis. 2023;10:362-377. 2. Cummings J et al. J Prev Alzheimers Dis. 2022;2:221-230.
• >4 microhemorrhages (defined as ≤10 mm at the greatest diameter)
• A single macrohemorrhage >10 mm at greatest diameter
• An area of superficial siderosis
• Evidence of vasogenic edema
• >2 lacunar infarcts or stroke involving a major vascular territory
• Severe subcortical hyperintensities consistent with a Fazekas score of 3
• Evidence of ABRA
• Evidence of CAA-ri
• Any other major intracranial pathology that may cause cognitive impairment (eg, cerebral contusion,
encephalomalacia, brain aneurysms or other vascular malformations, CNS infection, and brain tumors
other than meningioma or arachnoid cysts)
• MRI evidence of a non-AD dementia
Baseline MRI-Based Exclusion Criteria
2. Detecting, Monitoring, and Managing Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
3T scanner (recommended)
1.5T scanner (minimal)
High field strength scanners have greater sensitivity but limited availability
The use of 1.5T scanner is endorsed as a minimum standard
Slice thickness: ≤5 mm Thinner slices increase resolution, but decrease signal-to-noise ratio
TE: ≥20 ms Longer TE increases sensitivity to detection
2D T2* GRE or SWI
(for ARIA-H)
MRI sequences used to improve the detection, visualization, and monitoring of
microhemorrhages and superficial siderosis (ARIA-H)
T2-FLAIR (for ARIA-E) MRI sequences used to detect and monitor brain edema or sulcal effusion (ARIA-E)
Diffusion-weighted imaging
An MRI method used to differentiate between ARIA and cytotoxic processes (eg, infarcts)
Recommended for differential diagnosis
Visit the American Society for Neuroradiology (ASNR) website to access ARIA resources,
including links to standardized protocols for 3T and 1.5T scanners via this QR code or URL:
https://www.asnr.org/education-resources/alzheimers-webinar-series
MRI Acquisition Protocols to Detect and Monitor ARIA1-3
3. Detecting, Monitoring, and Managing Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
ARIA Type
ARIA-E
ARIA-H
microhemorrhage
ARIA-H superficial
siderosis
FLAIR hyperintensity
confined to sulcus and/or
cortex/subcortical white
matter in one location <5 cm
Mild Moderate
Radiographic Severity
Severe
≤4 new incident
microhemorrhages
One focal area
of superficial siderosis
FLAIR hyperintensity 5-10 cm,
or more than one site
of involvement, each
measuring <10 cm
5-9 new incident
microhemorrhages
Two focal areas
of superficial siderosis
FLAIR hyperintensity measures
>10 cm, often with significant
subcortical white matter
and/or sulcal involvement;
≥1 separate sites of
involvement might be noted
≥10 new incident
microhemorrhages
>2 focal areas
of superficial siderosis
Classifying ARIA by Radiographic Severity4,5
4. Detecting, Monitoring, and Managing Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
Headache
Confusion and
dizziness
Neuropsychiatric
symptoms
Nausea
Gait
disturbance
Visual
disturbance/
blurred vision
Seizure
Less frequent Uncommon
Symptom Severity
Mild
Discomfort noted;
no disruption of
daily activity
Moderate
Discomfort sufficient
to reduce or affect
normal daily activity
Severe
Incapacitating,
with inability to perform
normal daily activity
Symptoms Consistent With ARIA That Should Trigger Out-of-Sequence MRI6-8
5. Detecting, Monitoring, and Managing Amyloid-Related
Imaging Abnormalities (ARIA)
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
Baseline MRI has no exclusion factors
MRI routine or conducted because of symptoms suggestive of ARIA
ARIA-E or ARIA-H detected
Symptomatic Asymptomatic
Radiographically mild ARIA-E
or mild ARIA-H
Continue treatment with
anti-Aβ antibody; monthly MRI
Continue treatment;
discontinue monthly MRI if ARIA-E
resolves or ARIA-H stabilizes
Resume treatment with anti-Aβ antibody
Suspend treatment; clinical assessment;
repeat MRI monthly
Radiographically
moderate/severe ARIA-E
or moderate/severe ARIA-H
MRI shows resolution of ARIA-E or
stabilization of ARIA-H; symptoms
resolve; patient wishes to continue
Stop anti-Aβ antibody therapy for any of the following
• Any macrohemorrhage
• >1 area of superficial siderosis
• >10 microhemorrhages since treatment initiation
• >2 episodes of ARIA
• Severe symptoms of ARIA
• Patient requires treatment with an anticoagulant
Severity of Changes Observed on MRI
Radiographic ARIA-E: Mild
Radiographic ARIA-E: Moderate
Radiographic ARIA-E: Severe
Radiographic ARIA-H: Mild
Radiographic ARIA-H: Moderate
Radiographic ARIA-H: Severe
Symptom Description
No Symptoms Mild Symptoms Moderate Symptoms Severe Symptoms
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Discontinue dosing
Suspend dosing
Suspend dosing Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Suspend dosing
Discontinue dosing Discontinue dosing
Continue dosing
Continue dosing
ARIA Management Algorithm6-8
1. Cogswell PM et al. AJNR Am J Neuroradiol. 2022;43:E19-E35. 2. Sperling RA et al. Alzheimers Dement. 2011;7:367-385. 3. Barakos J et al. J Prev Alzheimers Dis. 2022;9:211-220.
4. Aduhelm (aducanumab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761178s007lbl.pdf. 5. Leqembi (lecanemab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269s000lbl.pdf.
6. Cummings J et al. J Prev Alzheimers Dis. 2023;10:362-377. 7. Cummings J et al. J Prev Alzheimers Dis. 2022;2:221-230. 8. Cummings J et al. J Prev Alzheimers Dis. 2021;4:398-410.
6. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
Parenchymal Edema
New T2-FLAIR hyperintense signal with mild local
mass effect and sulcal effacement measuring <5 cm
(mild ARIA-E)
New multifocal, patchy T2-FLAIR hyperintense
signal, each region measuring <5 cm (moderate
ARIA-E); multiple ARIA-E yields a classification of
moderate, as long as each region is <10 cm
Extensive T2-FLAIR hyperintense signal throughout the
right frontal and parietal lobes measuring >10 cm
(severe ARIA-E); associated mass effect and sulcal
effacement throughout much of the right hemisphere
Baseline Baseline Baseline
Post-treatment Post-treatment Post-treatment
Mild Moderate Severe
New sulcal T2-FLAIR hyperintense signal measuring
<5 cm in transverse dimensions (mild ARIA-E)
New T2-FLAIR sulcal effusion involving the right
posterior temporal and parietal lobes measuring
5-10 cm (moderate ARIA-E)
Extensive T2-FLAIR sulcal effusion involving the
bilateral temporal and occipital lobes measuring
≥10 cm in extent (severe ARIA-E)
Baseline Post-treatment
Mild
Sulcal Effusion
Baseline Post-treatment
Moderate
Baseline Post-treatment
Severe
ARIA-E Examples (Detected With T2-FLAIR Sequence)1
7. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
Microhemorrhage
Postdosing, ≥10 new microhemorrhages
(severe ARIA-H)
Baseline Post-treatment
Severe
Postdosing, 5 treatment-emergent
microhemorrhages (moderate ARIA-H)
Baseline Post-treatment
Moderate
Postdosing, few (<5) new peripheral left frontal
microhemorrhages (mild ARIA-H)
Baseline Post-treatment
Mild
Superficial Siderosis
Postdosing, new right temporal superficial siderosis, which involves
contiguous sulci when viewed over multiple slices (mild ARIA-H,
siderosis); this patient also had two treatment-emergent
microhemorrhages (mild ARIA-H, microhemorrhage)
Two regions of treatment-emergent superficial siderosis in the
right greater-than-left frontal lobes (moderate ARIA-H)
Baseline Post-treatment
Mild
Baseline Post-treatment
Moderate
ARIA-H Examples (Detected With T2-GRE or SWI Sequence)1
8. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
Infarct (Early Subacute)
FLAIR+ (hyperintensity)
• In addition to FLAIR and GRE/SWI sequences, a trace DWI
sequence should be included as routine protocol in ARIA
monitoring examinations to help with the differential
diagnosis of new signal abnormalities
• For example, the DWI sequence plays an important role in
helping to differentiate ARIA-E from potential cytotoxic
edema caused by an incidental infarct
• In classic cases of ARIA, the diffusion restriction will be
absent, because intense diffusion restriction associated
with an infarct is not a characteristic of ARIA
• The DWI sequence helped to identify the underlying
etiology of this patient’s radiographic findings
• Diffusion restriction was identified, which indicated that it
was not ARIA
• However, the diffusion restriction was located in the sulci,
which is not a typical pattern seen with acute or subacute
infarcts
• This patient was diagnosed with bacterial meningitis
following confirmatory lab testing
Infection (Bacterial Meningitis)
FLAIR+ (vasogenic edema
and sulcal effusions)
GRE/SWI+ (microhemorrhages
and superficial siderosis)
DWI+ (with restricted
diffusion in the sulci)
DWI+ (with restricted diffusion)
GRE/SWI+ (microhemorrhage)
ARIA Mimics2
9. Selected Images of Amyloid-Related Imaging
Abnormalities (ARIA) and Its Mimics
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
1. Cogswell PM et al. Am J Neuroradiol. 2022;43:E19-E35. 2. Images courtesy of Tammie L.S. Benzinger, MD, PhD.
ARIA Mimics2
Brain Metastasis
FLAIR+ (hyperintensity)
• New signal abnormalities detected in ARIA monitoring
examinations may require T1-weighted gadolinium-enhanced
imaging to differentiate between ARIA and brain metastases
• Contrast-enhanced imaging should be considered based on
the patient’s medical history and/or any clinical findings that
may suggest the possibility of a metastatic etiology
• ARIA and PRES are usually indistinguishable based on MRI (eg, both
will typically have FLAIR hyperintensities and no restricted
diffusion)
• Therefore, the clinical context is critical to differentiate between
ARIA and PRES
• This patient presented to the emergency department with
confusion, headache, and very high blood pressure (which is a
classic presentation for PRES)
• They were treated for their hypertension, which resolved their
clinical symptoms and their edema
Posterior Reversible Encephalopathy Syndrome (PRES)
FLAIR+ (hyperintensities) GRE/SWI negative DWI negative
(no diffusion restriction)
T1 postcontrast + enhancement
GRE/SWI+ (microhemorrhage)
T1 postcontrast
10. Use the following pages as reporting templates
to document baseline screening MRI prior to initiating
anti-amyloid therapy (page 1) and follow-up MRI
to monitor ARIA in patients undergoing
treatment with anti-amyloid therapy (pages 2-3).
Printable Resource
ARIA Reporting Templates
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/MCV40
11. Baseline MRI for Screening Prior to Initiating Anti-Amyloid Therapy (page 1 of 1)
Scan Information (fill in or circle response as needed)
DWI
Gadolinium
Contrast
ARIA–H
Sequence
ARIA–E
Sequence
Slice
Gap
Slice Thickness
(mm)
Field
Strength
Model
Manufacturer
Y
N
Y
N
SWI
GRE/T2*
3D T2-FLAIR
1.5T
3T
Hyperintensities/Infarcts Summary
Location
(eg, frontal, parietal, occipital, temporal,
brainstem, cerebellum)
L/R
Type
(eg, parenchymal; sulcal)
Max Diameter
(cm)
Lesion 1
Lesion 2
Lesion 3
Lesion 4
Microhemorrhages/Superficial Siderosis Summary
Brainstem
Deep Gray
Cerebellum
Temporal
Frontal
Parietal
Occipital
Total
MCH count
SS count
Findings
Total FLAIR hyperintensities: ______________
Describe locations and measure longest size in 1 dimension for each: _________________________________________________________________
Total microhemorrhages: ________________
Describe locations in general, deep vs lobar: ____________________________________________________________________________________
Total areas of superficial siderosis: __________________
Describe locations: _________________________________________________________________________________________________________
General description of other acute or chronic findings (eg, macrohemorrhage >10 mm; vasogenic edema; >2 lacunar infarcts or stroke involving a major
vascular territory; severe subcortical hyperintensities consistent with a Fazekas score of 3; evidence of ABRA; evidence of CAA-ri; evidence of non-AD
dementia; any other major intracranial pathology that may cause cognitive impairment):
_____________________________________________________________________________________________________________________________
_____________________________________________________________________________________________________________________________
IMPRESSION
Total microhemorrhages (circle one): 0-4 5-9 ≥10
Superficial siderosis (circle one): is not detected is present
Note any other EXCLUSION CRITERIA for initiating treatment with anti-amyloid therapy:
____________________________________________________________________________________________________________________
Restricted Diffusion
(circle correct response)
Contrast Enhancement
(circle correct response)
Yes No N/A
Yes No N/A
Patient Information
Patient name:____________________________ Age:________ Sex:_______
Patient ID:___________________ Referring MD:________________________
Report Information
Scan Date:_________________________________
Site Location:_______________________________
Updated findings were conveyed to _____________________________ by _______________________________
(referring physician) (radiologist)
12. Follow-Up MRI to Monitor for ARIA in Patients Undergoing
Treatment With an Anti-Amyloid Therapy (page 1 of 2)
Patient Information
Patient name:____________________________ Age:________
Sex:_______ Patient ID:___________________
Referring MD:___________________________________________
Purpose of scan (circle correct response): scheduled/asymptomatic monitoring for ARIA
OR unscheduled/safety MRI in response to symptoms
Report Information
Scan Date:________________________________
Site Location:______________________________
Scan Information (fill in or circle response as needed)
DWI
Gadolinium
Contrast
ARIA–H
Sequence
ARIA–E
Sequence
Slice
Gap
Slice
Thickness
(mm)
Field
Strength
Model
Manufacturer
Y
N
Y
N
SWI
GRE/T2*
3D T2-FLAIR
1.5T
3T
ARIA-E Summary
Location
(eg, frontal, parietal,
occipital, temporal,
brainstem, cerebellum)
L/R
Type
(eg, parenchymal;
sulcal)
Change
From
Baseline
(cm)
Lesion Dynamics
(eg, new, enlarging,
shrinking, stable
Max
Diameter
(cm)
Lesion 1
Lesion 2
Lesion 3
Lesion 4
Treatment History
Anti-Amyloid Agent: ________________________________ Number of doses received: ____________
Date of last dose: _______________________ Suspected ARIA Symptoms (if present): ______________________
Restricted Diffusion
(circle correct response)
Contrast Enhancement
(circle correct response)
Yes No N/A
Yes No N/A
13. ARIA-H Summary
Brainstem
Deep Gray
Cerebellum
Temporal
Frontal
Parietal
Occipital
Total
Current
MCH count
Baseline
MCH count
Change from
baseline
MCH count
Current SS
count
Baseline SS
count
Change from
baseline SS
count
Radiographic Severity (circle response)
ARIA Type
Severe
Moderate
Mild
≥1 location, >10 cm
1 location, 5-10 cm
OR
>1 location, each <10 cm
1 location, <5 cm
ARIA-E
≥10
5-9
0-4
ARIA-H
(MCH)
>2 focal areas
2 focal areas
1 focal area
ARIA-H
(SS)
Note other acute or chronic findings: _________________________________________________________________
_________________________________________________________________________________________________
Updated findings were conveyed to _____________________________ by _______________________________
(referring physician) (radiologist)
Follow-Up MRI to Monitor for ARIA in Patients Undergoing
Treatment With an Anti-Amyloid Therapy (page 2 of 2)
14. ARIA Standardized Reporting Template for PowerScribe
Full abbreviations, accreditation, and disclosure information available at PeerView.com/MCV40
Download the XML code for a standardized and automated ARIA reporting
template in PowerScribe by scanning the QR code or visiting the provided URL:
www.PeerView.com/ARIA24-PowerScribeXML
Once the file is downloaded, the code will need to be updated for your radiology department.