Update on ICH Imaging 2018congress.cnsfederation.org/course-notes/2018...Update on ICH Imaging 2018...

Update on ICH Imaging

2018 Richard Aviv

Professor Medical Imaging

Sunnybrook Health Sciences Center

University of Toronto, Canada

Disclosure

• Grant recipient (Paid to institution) from:

– Related

• Canadian Institute for Health Research

• Heart and Stroke Foundation of Ontario

– Unrelated

• PSI foundation

• AHSC AFP Innovation Fund, Ontario

Objectives

– Evidence for

• NCCT markers of Hematoma Expansion

• NCCT vs CTA predictors of HE

• Clinico-radiological scores

– Update on Clinical Trial results STOP IT,

SPOTLIGHT

– Delayed Imaging for secondary vascular

lesions

Role of Imaging

• Goal of imaging

– Diagnosis of ICH….. NCCT

– Primary versus secondary ICH…..CTA/ MRA

– Prediction of Hematoma Expansion

• NCCT

• Clinico-radiological scoring

• ICH 10-15% of strokes

CTA and contrast-enhanced CT may be considered to help identify patients

at risk for hematoma expansion (Class IIb; Level of Evidence B)

Stoke 2015; guidelines

AHA Guidelines 2015

NCCT markers of hematoma Expansion

Island Black

hole

Blend Swirl

Irregularity and heterogeneity

Fluid level


Island

1) ≥3 scattered small hematomas all separate from the main hematoma OR

2) ≥4 small hematomas some or all of which may connect with the

main hematoma

3) If connected should be bubble-like or sprout-like but not lobulated

Stroke. 2017;48:00-00. DOI: 10.1161/STROKEAHA.117.017985

16% ICH


Black hole

1) black hole encapsulated within the hyperattenuating hematoma

2) could be round, oval, or rod-like but not connected with the adjacent brain tissue

3) Identifiable border.

4) ≥28 HU difference between 2 density regions.

Stroke. 2016;47:1777-1781. DOI: 10.1161/STROKEAHA.116.013186.)

15% ICH


Blend

1) blending of hypo and hyper attenuating area

2) Well-defined margin ≥18 HU between regions

3) Hypo area not encapsulated by hyperattenuating region

Stroke. 2015;46:2119-2123. DOI: 10.1161/STROKEAHA.115.009185

17% ICH


Swirl

BMC Neurology 2012, 12:109

1) Region(s) of hypo or or isoattenuation (compared to the attenuation of brain

parenchyma) within the hyperattenuated ICH.

2) vary in shape and can be rounded, streak-like or irregular

30% ICH


Irregularity and heterogeneity

Stroke. 2009;40:1325–1331

Hematoma arising from a solitary focus: more regular edge vs multiple foci

Heterogeneous density reflects active hemorrhage, variable hemorrhagic time

course, and multifocality


Fluid levels

1) Correlated with anticoagulation treatments and lobar location

2) May reflect anomalies in the intrahemorrhage coagulation process

1-7% ICH

Stroke. 2015;46:3111–3116.


Hypodensities Island sign Blck Hole Sign Blend Sign Swirl Sign Irregular Shape Heterogeneous density

Year of

Publication

2016, Boulouis 2017, Li 2017, Li 2015, Li 2012, Sleariu 2009, Barras 2009, Barras

Study Design Single Center,

retrospective

Single Center,

prospective

Single Center,

prospective

Single Center,

retrospective

Single Center,

retrospective

MultiCenter,

retrospective

MultiCenter,

retrospective

Sample Size, n 1029 252 206 172 203 90 90

Time window 48h 6h 6h 6h <2h,2-24h

and>24h

6h 6h

Marker’s

Prevalence

31.2% 16.30% 14.6% 16.9% 30% n/a n/a

Inter-rater

reliability

K=0.87 K=0.91 K=0.81 K=0.96 K=0.8 Weighted K=0.61 Weighted K=0.61

ICH Expansion

Definition

>33% or 6ml >33% or 6ml >33% or 12.5ml >33% or 12.5ml None Conituous scale

and >33% or

12.5ml

Conituous scale and

>33% or 12.5ml

EXPANSION PREDICTION

Sensitivity 0.62 0.45 0.32 0.39 n/a n/a n/a

Specificity 0.77 0.98 0.94 0.96 n/a n/a n/a

PPV 0.40 0.93 0.73 0.83 n/a n/a n/a

NPV 0.89 0.78 0.73 0.74 n/a n/a n/a

Multivariable OR

(95% CI), P Value

3.42(2.21-5.3),

p<0.001

3.51 (1.26-9.81)

p<0.0001

4.12 (1.44-11.77)

p=0.008

20.23 (5.13-

79.77)

p<0.001

n/a OR n/a, p=0.159

OR n/a, p=0.796

OR n/a, p=0.046

OR n/a, p=0.273

Development

plus replication

cohort

Swirl sign

associated with

Poorer outcome,

larger ICH

volume, higher

mortality

Retrospective

analysis of data

from a phase iib

RCT, shape rated

on 1-5

catagorical scale

Retrospective analysis

of data from a phase

iib density rated on 1-5

catagorical scale

Modified from Stroke 2017;48:1120

Clinicoradiological scores (NCCT)

Stroke. 2018 May;49:1163, Stroke 2015;46:376, Clinical Neurology and Neurosurgery 2013;115:1028

BAT score (2018) Hematoma Expansion

Prediction Score (2015) Takeda (2013) 24 point score

(BRAIN)

Development cohort 344 237 201 964

Validation cohort PREDICT, ATTACH 2 n=1195 (2

cohorts) Bootstrapping Not validated INTERACT1 (346)

HE definition >6ml or >33%; <=24hrs >6ml or >33%; <=72hrs >33% or >12.5 ml; <=24 hours >6ml or >33%; <=24hr

Score range 0-5 0-18 N/A 0-24

Study of NCCT density Yes Yes Yes

Score Components Blend sign Antiplatelet use ICH Volume >16cc Baseline ICH vol <10, 10-20,>20

Any Hypodensity SAH presence ICH Heterogeneity Warfarin use

Time Onset to scan <2.5 Time Onset to CT <3 Elevated sBP (1.5h) >160 Time Onset to CT (hrs)

- GCS - IVH extension Y/N - Current Smoking - Recurrent ICH - history dementia - -

C statistic 0.70 (0.64-0.77) 0.76 (0.69-0.83) AUC = 0.91 AUC 0.67 (0.61-

0.74)

Sensitivity 0.70 (0.58-0.81) - - -

Specificity 0.64 (0.56-0.71) - - -

PPV 0.45 (0.35-0.54) - - -

NPV 0.84 (0.76-0.90) - - -

Exclusion Anticoagulated pts - GCS<=3

large ICH volumes >60cc Surgery prior to follow up Surgery prior to follow up

HT ischemic stroke HT ischemic stroke -

AVM AVM AVM

Isolated IVH Isolated IVH -

Inclusion <6 hrs <12 hrs <6 hrs

INR<1.5 deep ICH

Notes ICH heterogeneity/

irregularity not predictive ICH irregularity not

predictive

Spot Sign: Experience >1000 patients

• Predictor of:

– Hematoma expansion

– Mortality

– Poor outcome

– Longer hospital stay

Stroke 2007;38:1257. Neurology 2007;68:889. AJNR 2008;28:520. Stroke 2010;41:54. Stroke 2011;42:3441, Lancet Neurology 2012,

Cerebrovasc Dis 2013; 35:582

Overall performance for hematoma expansion

Sens 50-93%, Spec 50-93%, NPV 80-98%, PPV 24-77%

• Single or multiple, serpiginous or spot-like foci of contrast density

• No density present on non contrast CT

• Within the margin of a parenchymal hematoma without connection to outside vessels

• (Hounsfield unit density at least double that of background hematoma- arterial density)

CTA Spot Sign

Stroke 2007;38:1257

NCCT

14:43

CTA

14:47 PCT

14:49 Spot Sign with active extravasation

83F facial droop, left weakness

Spot versus NCCT markers

• AUC Spot 0.73 vs Blend 0.662

1. Stroke. 2015;46:3111 2. Medical Science Monitor 2017;23:2250

N=311

Clinicoradiological scores (CTA)

Meta-analysis Lancet

Neurology (submitted)

Predict A/B 9-point score

Development cohort Pt level data n=5076 Prospective multicenter Single center, retrospective

Validation cohort validation prospective External validation prospective

HE definition >6ml >6ml or >33%; <=24hrs

>6ml or >33%; <=24hr

Score range A:0-23, B: 0-28 0-9

Study of NCCT

density Score Components Baseline ICH vol A: GCS ≤13, >13 or B: NIHSS

≤4,5-14,≥15 Baseline ICH vol <30,30-60,>60

Onset to CT Onset to CT (hrs) Onset to CT <=6,>6

antiplatelet use Warfarin use Warfarin use

anticoagulant use CTA spot Number 0,1, ≥2

CTA Spot present/ absent/unavailable

(CTA Spot present/ absent) - -

- -

C statistic 0.78 (1.96-6.16) CTA Spot added 0.83 (0.80-0.86)

A: AUC 0.78 (0.73-0.84) B: AUC 0.77 (0.71-0.82)

AUC 0.71 (0.65-0.77)

Notes A: Improved performance over 9 and 24 point score

Improved performance over CTA Spot alone

Spatial Correlation between

NCCT makers and CTA • N=40; Only 35% correlated1

• Added benefit of including both? 2

1. JAMA Neurol. 2016;73:961–968 2. JNNP submitted

Spatial Correlation between

NCCT makers and CTA • N=40; Only 35% correlated

• Added benefit of including both?

JNNP submitted.

• N=110 (55 Spot + each arm)

The SpoT sign fOr Predicting and treating ICH growTh study: STOP-IT SPOTRIAS/NINDS www.stopitstudy.com

‘SPOT sign’ seLection of Intracerebral hemorrhage to Guide Hemostatic Therapy: SPOTLIGHT CIHR www.stoplightstudy.com

• N=184 (Spot + and –)

• N=100 (50 Spot + each arm)

• www.stopauststudy.com

Therapeutic intervention vs markers

• CTA spot +ve randomized rVIIa (80

mcg/kg) or placebo ≤6.5hrs from onset • (STOP-IT Spot –ve controls)

– STOP-IT 12 US/Canadian sites

– SPOTLIGHT 14 Canadian Sites

• CT head pre-dose and 24 hrs

– Primary outcome ICH volume 24hrs

– Secondary outcome IVH vol, tICH vol, 90d

mRS

Stop-It and SPOTLIGHT

n=93

Hematoma Expansion

in the Spot Sign Negative Patients

Spot Positive Placebo Group

(n=37)

Spot Negative Group (n=72)

P-

value

ICH volume, median (IQR)

Baseline: 20 ml (9-33)

24h: 29 ml (14-52)


24h: 13 ml (6-23)

0.013

Total (ICH+IVH) volume, median (IQR)


24h: 31 ml (16-30)


24h: 14 ml (8-27)

0.0045

% patients with >6 ml or >33% increase in ICH

43% 11% 0.0003

The spot sign predicted final ICH volume (p=0.014) and mRS 5-6

(p=0.008) after adjustment for baseline ICH volume and onset to CT time

ISC 2017

Hematoma Expansion

in the Spot Sign Positive Patients

No significant treatment effect of rFVIIa on (log transformed)

follow up (t)/ICH volume, after adjusting for baseline ICH

volume, and onset to Rx ISC 2017

TICH 2 • Double-blind, randomised, placebo-controlled, parallel group, phase

3 trial (n=2325; 124 sites, 12 countries, 55 months)

• Tranexamic acid within 8 hrs, 1g/10m and 1g/8hrs.

• NCCT baseline and 24hrs

– CTA 11% of cases

– Onset to enrolment 3.6h

• Lower predefined safety outcomes in TXA group

CTA 17/2 DSA 22/2

“Reference standard”

Importance of delayed Imaging • 49 ♂

22 Feb 25 Feb 25 Feb

Courtesy Sanne Jacobs, University of Toronto fellow

Importance of delayed Imaging 25 Feb 25 Feb 28 May

5 June

Courtesy Sanne Jacobs, University of Toronto fellow

Results Sample size n=335 [Macrovascular cause in n=123 (37%)]

CTA- n=188 [29] CTA+ n=101 [94]

Early*² DSA n=89 [22]

Follow-up DSA n=16 [6]

Late DSA n=14 [1]

*¹ Typical location ICH = Basal ganglia/thalamus & brainstem

*² Early= <14 days

*³ 4 cavernoma, 1 Aneurysm, 1 dAVF, 5 AVM

n=78 [11]

n=11 [11*³]

n=5 [5] n=11 [1]

n=1 [1] n=13 [0]

>45 years, Typical location ICH*¹ & Hypertension

n=46 [0] n=289 [123]

CTA- n=50 [0]

CTA+ n=0 [0]

YES NO

Courtesy Aditya Bharatha, St Michael’s Hospital, Toronto

6%

6% 5 AVMs

AVM

ICH/IVH CTA

ICU admission, DSA, +/- INR, +/- NSx

ICU admission, +/- NSx consult (large hematomas),

early repeat imaging (24 hr or less NCCT), +/- MRI

Negative CTA

Hypertensive, older, and/or

typical ICH location?

24 hr

NCCT

<2d MRI

Tumor

Hemorrhagic infarct

Cavernoma

Microbleeds

Amyloid

HTN

Younger, Isolated

IVH, Lobar

non-HTN,

No anticoagulation

Strongly

consider DSA Consider DSA

MRI 6-8

weeks

Vascular

lesion

Spot sign

positive

24 hr NCCT

Yes No

Negativ

e Negativ

e AJNR 2013;34:1481

-ve

+ve

Acknowledgements • CT Techs Sunnybrook Health Sciences Center

• Grant Support – Heart and stroke Foundation of Ontario

– CIHR

• Research Assistants

• Dept of Medical Imaging and Division of Neuroradiology Sunnybrook

– Sean Symons, Robert Yeung, Peter Howard, Matylda Machnowska, Pejman Maralani, Chris Heyn

• Dept of Neurology and Neurosurgery – David Gladstone, Rick Swartz, Julia Hopyan, Erin Dyer, Leo da Costa, Victor Yang

[email protected]

Spot Sign training: www.stopitstudy.com

Update on ICH Imaging 2018congress.cnsfederation.org/course-notes/2018...Update on ICH Imaging 2018...

Documents

Transcript of Update on ICH Imaging 2018congress.cnsfederation.org/course-notes/2018...Update on ICH Imaging 2018...