Focus on Imaging Science

assoverwroughtAI and Robotics

Nov 6, 2013 (3 years and 8 months ago)

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NIBIB Strategic Plan:
Focus on Imaging Science

Belinda Seto, Ph.D.

Deputy Director

National Institute of Biomedical
Imaging and Bioengineering

Goal One


Improve human health through the
development of emerging biomedical
technologies at the interface of engineering
and the physical and life sciences.


2 examples: represent the convergence of
bioengineering, physical sciences, biology and
clinical sciences


Molecularly
-
Targeted Fluorescent Cell Penetrating Peptides for
Tumor and Nerve

Quyen

Nguyen et al.
Nature Biotechnology
(NIBIB K08
Awardee
)

©2004 by National Academy of Sciences

Schematic diagram of
activatable CPPs. Cellular
uptake induced by a cationic
peptide is blocked by a short
stretch of acidic residues
attached by a cleavable linker.

Surgery Guided with
Molecularly
-
Targeted
Fluorescence of Both Tumor and
Nerve

Quyen

Nguyen et al.
Nature
Biotechnology

(NIBIB K08
Awardee
)


Portion of nerve embedded within tumor visible
with
fluorescently labeled probe.
Tumor and nerve
both invisible in standard white light reflected
image

Deep red Cy5
fluorescence from tumor
-
targeting
ACPP pseudocolored
green

and overlaid on standard
white
-
light reflectance image

Green

FAM fluorescence from
nerve imaging peptide
pseudocolored
aqua

Buried nerve branch

Diagram of the
transcranial

MRI

guided focused ultrasound surgery device for noninvasive brain
tumor ablation being developed under R01EB003268, (PI: K.
Hynynen
). This work evaluated the
clinical

feasibility of
transcranial

magnetic resonance imaging

guided focused ultrasound surgery
(
McDannold

et al, ). This work was also based on earlier funding by NCI grants: CA76550;
CA089017; CA46627

Transcranial

MRI

Guided Focused Ultrasound Surgery of
Brain Tumors: Initial Findings in 3 Patients

(
Neurosurgery 66:323
-
332, 2010)

NIBIB Translation Research: World’s First MR
-
Guided HIFU Treatment for Essential Tremor



Helmet
-
like applicator developed with 512 phased
-
array HIFU transducers



Can be precisely focused within the brain.



Entering FDA clinical trials

PI on this study: W.
Jeffrey Elias, MD.,
U.Va.

Funded by the
Focused Ultrasound
Foundation.

K.Hynynen, U. Toronto, funded
by NIBIB, collaborated with
InSightec in adapting the
design of the applicator and
US delivery, based on research
funded under R01EB 3268,

ExAblate

MR
-
guided High
-
Intensity Focused Ultrasound (
Insightec, Inc.)

Magnetic Resonance
Elastography



Hard

Soft

In principle, the mechanical properties of tissue could be
assessed if a method could be developed to visualize
propagation of applied mechanical waves

The challenge in visualizing such waves is that they are
only microns in amplitude. How can such small motions
be reliably imaged?

Magnetic resonance imaging is a remarkably versatile technology.
A 1995 publication by Mayo Clinic researchers reported the
discovery of a method to visualize propagating shear waves in
tissue with amplitudes smaller than the wavelength of light…

MR
Elastography

Tissue
-
simulating gel
phantom with stiff
inclusions

80

0

40

-
10

0

+10

1. Driver

2. MRE Sequence

3. Inversion

(30
-
500 Hz)


2.5cm

Conventional

MR Image


Wave Images

Displacement (mm
)

Shear Stiffness (
kPa
)

Elastogram

Importance of Chronic Liver Disease,
Fibrosis, Cirrhosis


A leading cause of death world
-
wide


Increasing prevalence of conditions
that cause hepatic fibrosis


Hepatitis C
-

170 M people
globally


Hepatitis B


Obesity / Fatty liver disease


Fibrosis can be reversed, if
diagnosed early and treated

Progression of Liver Disease



Risk of Complications



Potential Sampling Errors



Subjective Histology Grading

Liver Biopsy


Standard Diagnostic Procedure to rule
-
out
Fibrosis

Irreversible
High Mortality

Reversible
Silent

Normal

Cirrhosis

Fibrosis

Technology Developed for Hepatic MRE

-
90

0

+90

Displacement (
m
m)

Shear Stiffness (kPa)

0

10

4

6

8

2

Elastogram

Active Driver

Acoustic waves at 60Hz

Imaging time: 16 sec

Passive Driver

(EB001981)

+60

-
60

Amplitude (
m
m)

0

M, 21 yrs



-
60

+60

Amplitude (
m
m)

0

F, 30 yrs


2.0 kPa

7.0 kPa

Biopsy: Grade 3 Fibrosis

Healthy

Chronic Liver Disease

Goal Two


Enable Patient
-
centered health care
through development of health
informatics and mobile and point
-
of
-
care
technologies



Example: Image sharing contracts

Image Data Sharing: NIBIB Activities


Contract awarded to Radiological Society of
North America: Image Sharing Network,
PI: Dr. David Mendelson


Grant awarded to Wake Forest University


Grant awarded to University of Alabama

Goal Three


Transform advances in medicine at the molecular
and cellular levels into therapeutic and diagnostic
technologies that target an individual’s personal
state of health



Example: Mehmet Toner’s project on circulating
tumor cells

Key dimensions of the CTC
-
chip


45
m
m

Biotinylated

anti
-
EpCAM

Avidin

Capture
Antibody

Clinical Application

EpCAM

Lung, Prostate, Colon,
Pancreas, Breast

EGFR

Lung, Brain, Colon

HER
-
2

Breast

CD133

Lung, Prostate

CD44,
CD44v6

Lymphangioleiomyomatosis


NG2

Angiomyolipoma
,
Melanoma

OH

OH

OH

OH

OH

OH

OH

Native Signal

Filter

f

(
x,y
)

Quantify

(x
3
, y
3
)

(x
2
, y
2
)

(x
1
, y
1
)

Threshold

DNA

Classify

CTC

PSA

Automated Image Processing


Stott, et al. Science Translational Medicine, 2010



Enumerate



Report



Image database



Intensity
-
based



Brightest signals



Center of mass (x
i
,y
i
)



Area



Elongation factor




|(x
1
,y
1
)


(x
2
,y
2
)| < 2.5
µ
m



Elongation < 3.6



Area
PSA

> Area
DNA




12
-
bit monochrome



Filter
-
based images

Taking Imaging Beyond Enumeration

Novel classification schema for CTCs using cross
-
correlation image processing algorithms





Ki67: Cell proliferation marker

M30: Cell apoptosis marker

Questions to be addressed:

1.
Can CTCs be detected in the blood of
patients with EGFR
-

and ALK
-
mutant
lung cancer?

2.
Do CTC numbers change with
treatment?

Numbers

4.
Can signaling be measured in CTCs
(and does it change with targeted
therapy)?

5.
Do the signaling effects in CTCs match
those of the primary tumor?

6.
Does this predict clinical outcome?

Signaling

3.
Can tumor
-
specific mutations be
detected in CTCs?

Genotype

Dynamic Range of CTC Enumeration

Lung Cancer Patient Responding

Lung Cancer Patient Not Responding

CTC Numbers Track with Disease
Course


Nagrath

et al,
Nature
2007

Goal Four


Develop medical technologies that are low
-
cost,
effective, and accessible to everyone.


Example:

GE
Vcan


Transformative low cost mobile clinical
Ultrasound system. A hand held portable $8K
device that can be carried in a coat pocket and
has the same functionality of conventional
systems which cost ~$200K . Has been embraced
by leading cardiologist as a major development
to help realize
mHealth

and is described as
tomorrow’s stethoscope.


GE V
-
scan: World’s smallest portable
ultrasound

V
-
scan offers a chance for physicians to make a
move from stethoscopes to portable imaging
devices, bringing advanced visualization to any
examination room. V
-
scan can offer an
immediate look beyond patient vital signs with
the potential to identify critical issues, like fluid
around the heart, which could be a sign of
congestive heart failure. And for cardiologists,
Vscan provides a dependable visual evaluation of
how well the heart is pumping at a glance, so
they can treat patients more efficiently.

GE’s Chairman and CEO Jeff Immelt demonstrates

the new V
-
scan

The handheld ultrasound can reduce the need for specialist
referrals, which in turn can lower healthcare costs.

NIBIB Grant R01EB002485: Kai Thomenius, Ph.D.

Goal Five


Develop training programs to prepare a
new generation of interdisciplinary
engineers, scientists, and health care
providers.



Examples: R25 program for residents

NIBIB Research Education Program for
Residents and Fellows (R25)


Target groups: residents or fellows interested in
developing research experience in
interdisciplinary areas such as quantitative
biology, biologically
-
inspired engineering, and/or
imaging science

.


12 month initial support, additional 12 months
possible


75% effort


$70,000 direct costs including $10,000 research
supplies and $1000 travel

Goal Six


Expand public knowledge about the medical,
social, and economic value of
bioengineering, biomedical imaging, and
biomedical informatics.



Examples of start
-
ups