Download Multiparametric and multimodality imaging to identify radiological

Multiparametric and Multimodality Imaging to
Identify Radiological Biomarkers for Treatment Response
Michael A. Jacobs1,2, Vered Stearns2, Katarzyna Macura1,
Antonio C. Wolff 2, Ihab Kamel1,
Richard Wahl1, David A. Bluemke1,3
1The
Russell H. Morgan Department of Radiology and Radiological Science, 2Sidney Kimmel Oncology
Department, and 3NIH Clinical Center
The Johns Hopkins University School of Medicine, Baltimore, MD
Response Evaluation Criteria in Solid Tumors (RECIST)
and
World Health Organization
• RECIST
• Unidimensional measurement of the greatest diameter of the lesion
(≥10mm, limited to 5 lesions)
•Metastatic Lesions - (≥10mm)
•Non-measurable – ≤10mm lesions, leptomeningeal, organomegaly,
etc….
• WHO
• Bidimensional measurement of the greatest diameter of the lesion
(≥10mm, limited to 5 lesions per organ)
• Measurable Disease
Therasse P, et al. J Natl Cancer Inst. 2000 Feb 2;92(3):205-216.2.
WHO handbook for reporting results of cancer treatment. Publication No. 48; 1979
Clinical and Pathological Response
• Clinical Response
• cCR- no palpable tumor
• pCR- a decrease in palpable tumor by 50%
• nCR – no decrease in palpable tumor
• Pathological Response
• cPR- as no viable invasive cancer (macro or microscopically) in the pathologic
specimen
• pPR- a considerable reduction in tumor cells but presence of ≤10% microscopic foci
of invasive cancer cells could be detected.
• nPR - specimens that did not meet the criteria for the above
Current State of the Art Methods for
Radiological Methods of Treatment Response
Current State of the Art Methods for
Radiological Methods of Treatment Response
1.
Breast Imaging
»
2.
3.
4.
5.
Multiparametric MRI Breast Imaging
»
Detection and Characterization
»
Monitoring treatment response
Positron Emission Tomography/Computed Tomography (PET/CT)
»
Staging
»
Monitoring treatment response
Whole Body MRI
Integration of Multiparametric Radiological Data
»
6.
Mammography, US, MRI
PET/CT, MRI, others
Advanced Methods and Applications to Radiology and Beyond
PET/CT
•
Positron Emission Tomography/Computed Tomography
(PET/CT)
»
Detection and Characterization – Staging of Primary Disease
»
18FDG
»
Monitor Treatment Response (usually mid treatment)
(Fludeoxyglucose)
Multimodality Data Acquisition
• PET/CT Parameters
18FDG
or others
Dose (mCi) = Weight (kg) * 0.22(mCi/kg
» Range 5mCi-25mCi
Standardized Uptake Value Lean (SUV)
Positron Emission and Computed Tomography: PET/CT
18FDG
511 kev +
-o
PET
511 kev
180
CT
Radiotracer
PET/CT Images
Baseline
1st Cycle
SUV Max 31
SUV Max 9.9
Note: Skeletal enhancement due to G-CSF
Multiparametric Breast MR Imaging
• Multiparametric Breast MR Imaging
»
Detection and Characterization – Multicentricity or contralateral lesions
»
T2w, T1w : Anatomical
»
DWI with ADC mapping – Cellularity and water movement
»
DCE with pharmacokinetic analysis (PK) – Vascular profile
»
Spectroscopy – (Choline – 3.2 ppm) Metabolic profile
»
Sodium – Biochemistry profile
T1- and T2-weighted Imaging
T1WI
»
»
Can define glandular from fatty tissue
Can be used to define breast density
T2WI
»
»
»
Defines area of “bulk” edema
Differentiate cysts for other lesion in the breast
Assist in defining fibroadenomas
Dynamic Contrast
Dynamic Enhancement
Contrast PK Patterns
Dynamic Contrast PharmacoKinetic analysis (PK)
initial
delayed
persistent
fast
plateau
SI
medium
washout
slow
Time
A.
Malignant
B.
Benign
C.
Diffusion Weighted Imaging
Diffusion Weighted Imaging
Normal tissue
Tumor
H20
H20
H20
Increased cellularity and reduced extracellular space = restricted diffusion
Diffusion “b” value
The parameter that determines the diffusion sensitivity is known as “b” value
b value equation:
» (b=γ2G2δ2 (∆-δ/3)
γ= gyromagnetic ratio, G=gradient strength, δ=diffusion gradient duration, ∆= time between
diffusion gradient pulses
600
500
400
RF pulse
Diffusion
Gradients
SI
δ
300
200
100
∆
Si = So e
 n

−  ∑ bADC 
 i

0
-50
550
b values
Si 

ln

n
S
o
ADC = ∑ 
bi
i =1
1150
Diffusion Weighted Imaging
b=0
b=500
b=750
600
500
400
SI
T2WI
300
ADC map
200
Dynamic Contrast MRI
100
Low ADC
0
-50
550
b values
High ADC
1150
b=1000
harmacokinetic Color
map
B
ADC map
C
% enhancement
T1 High resolution
Subtraction
450
400
350
300
250
200
150
100
50
0
ADC value 1.05
Normalized ADC 0.44
E
Permeability histogram
Kinetic Curve
Type 3
0
45 90 135 180 225 270 315 360
Time
F
EVF histogram
Sodium Imaging
Outside
Na+
Na+
Na+
H+
H+
Na+
H+
H+
H+
Inside
Na+/K+ pump: Active Transport
Na+/H+ pump: Antiport
– provides information about metabolism or physiology
– Increased sodium concentration with pathology
– provides additional tissue contrast
Diffusion Weighted Imaging
T1WI
b=500
b=1000
b=750
Malignant
High
Low
T2WI
Low ADC
High ADC
ADC map
Dynamic Contrast MRI
Benign
Sodium map
Multiparametric and Modality Data Acquisition
MRI Parameters
T1 FSPGR (TR/TE = 250/4.2)
Fat Suppressed T2 FSE (TR/TE =5700/102)
3D FSGPR, pre/post 0.1mM/kg Gd
» 15 sec resolution,
» (TR/TE =20/4) (2 x 0.4 x 1.1mm3)
DWI Imaging
»
TR/TE =5000/90ms,
»
Multiple b values
Sodium Imaging
»
Twisted Projection Imaging
»
TE/TR =0.37/120ms
Spectroscopy
PET/CT Parameters
18FDG
Dose (mCi) = Weight (kg) * 0.22(mCi/kg
» Range 5mCi-25mCi
Standardized Uptake Value Lean (SUV)
Neoadjuvant Treatment
Multiparametric MRI and PET/CT as described previously
Patient Profile
» Operable Breast Cancer
» Primary Systemic Tx - AC (doxorubicin {60mg/m2} +
cyclophosphamide {600mg/m2 intravenous (IV)}) every 21 days x 4
cycles (~12 weeks), followed by Taxotere (docetaxel:100mg/m2 IV)
every 21 days x 4 cycles (~ 12 weeks).
Treatment Response determined at surgery
Multiparametric/Multinuclear and Multimodality studies for Chemotherapy
Exam 2
(repeat biopsy)
Baseline
•Cycle 1
•Cycle 2
Exam 4
•Cycle 3
•Cycle 4
Final
Time
Chemotherapy →
Exam 3
Exam 1
Multiparametric MRI and PET/CT
*baseline biopsy
**If metastatic – WB-MRI
Exam 5
DCE-MRI Volumetrics
Baseline
1st cycle (7 days) 4th cycle (5 days)
Before surgery
DCE MRI
MRS
Sodium Images
Lesion
Choline
Lesion
Baseline
5.0
4.0
3.0
2.0
1.0 PPM
Final Histology
5.0
1st cycle( 7 days)
4.0
3.0
2.0
1.0 PPM
pCR
Before surgery
5.0
4.0
3.0
2.0
1.0 PPM
DCE MRI
MRS
Sodium Images
Choline
Lesion
Baseline
PPM 5.0
4.0
3.0
2.0
1.0
0.0
Final Histology
Tx 3 (14 days)
PPM
Last Tx (before Surgery)
5.0
4.0
3.0
PPM5.0
4.0
3.0
2.0
1.0
pNR
2.0
1.0
0.0
Baseline
CT
PET
A.
PET/CT
Benign
B.
Malignant
Dynamic Contrast Enhanced-MRI
C.
Sodium
1st Cycle (7-8 day)
CT
A.
PET
PET/CT
Benign
B.
Malignant
Dynamic Contrast Enhanced-MRI
C.
Sodium
Baseline
CT
PET
A.
PET/CT
Benign
B.
Malignant
Dynamic Contrast Enhanced-MRI
C.
Sodium
1st Cycle (7-8 day)
CT
PET
A.
Benign
PET/CT
B.
Malignant
Dynamic Contrast Enhanced-MRI
C.
Sodium
A. Baseline Imaging
PET/CT Images
Lesion
DCE MRI
Lesion
DCE-PK
ADC Map
ADC Map
DCE-PK
PET/CT
1st Cycle (Day 7)
DCE MRI Response
Lesion
Malignant
DCE MRI
Lesion
Benign
Baseline
DCE-PK
Malignant
Lesion
Benign
ADC Map
After 1st Cycle
Newer Concepts and Methods
•
Whole Body MRI
•
Integration of Multiparametric Radiological Data
»
•
PET/CT, MRI, others
Advanced Methods and Applications to Radiology and Beyond
Coronal Scout
I
II
III
IV
V
VI
I
II
III
IV
V
VI
Sagittal Scout
T2WI
T1WI
Demonstration of the
Excellent anatomical and
functional information from
WB-MRI
ADC maps
T2w Images – Metastases noted on multiple coronal slices
Slice 16
Slice 18
Slice 21
Slice 26
DWI (b=800) – Metastases noted on multiple coronal slices
Slice 16
Slice 18
Slice 21
Slice 26
ADC Maps – Metastases Seen on Multiple Coronal Slices
Slice 16
Slice 18
Slice 21
Slice 26
3D-rendering
b=50
b=400
DWI
b=800
b=50
ADC map
b=400
b=800
Treatment monitoring - Baseline
T2WI
R
DWI
L
ADC map
PET
T2WI
WB-DWI
Baseline
Follow up
b=800
ADC map
WB-MRI
PET
DWI
T2W
b=50
b=400 b=800
T2WI
b=0
DWI
b=400
b=800
ADC Map
CT
PET
DWI
ADC map
b=50
b=300
b=600
PET/CT
T1
PET
CT
PET/CT
PET/MRI
WB-MRI
Courtesy : Dr. David Bluemke
Imaging Integration Using Manifold Learning
Contribution Scattergram: Recognition of similarity in data
Applications:
1) One-by-one contribution of Radiological Parameters in the lesion tracking
2)Track changes before, during and after treatment (therapy monitoring)
y2
y1
Treatment Response-Breast
Baseline
T1
T2
b0
b1000
ADC
Pre
Post
Sub
1st Cycle
T1
T2
b=0,250,500,750
ADC
Pre
Post
Sub
Contribution Scattergram
Baseline
1st
Combined: baseline and 1st treatment
Contribution Scattergrams
2D
3D
Displacement: A New Metric?
Treatment effect ranking:
1) b-highest(33%)
2) b-lowest(25%)
3) ADC(17%)
4) T2(25%)
5) Post(8%)
6) T1(5%)
7) Sub(4%)
8) Pre(3%)
3D Heat Map
T1b
T2b
b0b
b1000b
ADCb
Preb
Postb
Subb
T1s1
2 (5%)
T2s1
b0s1
b750s1
ADCs1
Pres1
Posts1
Subs1
11(25%)
15(25%)
10(33%)
7(17%)
1(3%)
3(8%)
2(4%)
Summary and Future Work
1.
Move beyond Traditional Radiological Metrics for Treatment Response
2.
Functional metrics defined by multiparametric and multimodality
Imaging (MRI/PET/CT)
»
DWI/ADC - ADC Map values
»
PK-DCE – Ktrans, Kep, Ve (extravascular space)
»
PET- SUV
3.
Whole Body PET/MRI
4.
Integration of all radiological data with other biomarkers
»
PET/CT, MRI, Serum, Genomic data, etc…….
Acknowledgements
David A. Bluemke
Zaver Bhujwalla
Paul Bottomley
Nancy Davidson
David Eisner
Riham El Khouli
Laura M. Fayad
Jonathan S. Lewin
Katarzyna Macura
Ronald Ouwerkerk
Li Pan
Ihab Kamel
Richard Wahl
Vered Streans
Antonio C. Wolff
The Money (while it lasts!)
P50CA103175, U01CA070095, and U01CA140204.