UC DAVIS CANCER CENTER

UC DAVIS CANCER CENTER

Endoscopic Enhancement by a
Spectroscopic Cancer Detection System
Ralph W. deVere White, M.D.
Professor and Chairman, Department of Urology
Director, UC Davis Cancer Center
University of California, Davis Medical Center
Stavros Demos, Ph.D.
Associate Professor, UCD Davis Medical Center
Senior Scientist, Chemistry and Material Sciences
Lawrence Livermore National Laboratory

ENDOSCOPICALLY DETECTED
TARGET CANCERS
• Colon (Lower GI)
• Lung CA
• Upper GI
• Bladder

Unanswered Endoscopic Questions
• Is what you see cancer?
• How deep does the cancer go?
• Have you removed all cancer?
Our Spectroscopic Cancer Detection System will
definitively and rapidly answer these questions,
reducing cost and increasing patient satisfaction.

Spectroscopic Cancer Detection System
Will Revolutionize Diagnosis and Treatment of
Colon, Bladder, Lung, and Gastro Intestinal Cancer
• Real Time (in vivo)
• Subsurface
• Outpatient
• Reduces Current Cost
• Patient / Hospital / Insurance Driven
• Will Not Radically Change Work Flow

SPECTROSCOPIC CAMERA
and CYSTOSCOPE

SPECTROSCOPIC CANCER
DETECTION SYSTEM
Camera
Camera
Box
Integration
Software
Light
Source

TESTING ORGAN SITE
TCC of the BLADDER
• 55,000 cases per year in U.S.
• 75% superficial cancer
• 50% Recur
- ⅓ due to undetected CA at
initial treatment

CURRENT PROBLEMS in
PROBLEMS
ENDOSCOPY
Delayed Diagnosis
OR is Labor Intensive
Patient Anxiety
OR/Biopsy Additional Costs
Failure to Determine Margin Status at
Time of Surgery and Detection of
Residual Disease
Have to wait 2-72
7 days for biopsy results
Adversely affecting pts, their families,
doctors, health systems, and payors
Delay in diagnosis after viewing the
worrisome pictures on TV monitor
$12,000
Necessitates future operations

Can we do this using photons?
Light can be used to probe both, structure and
biochemical composition of the tissue.
10
Hemoglobin
Water
1
Absorption
.1
.01
“OPTICAL WINDOW”
We use
this
range
.001
400
600
800
Wavelength
Absorption of light by tissue limits its penetration depth except
in the Near Infrared (NIR) spectral region where photons can
propagate 1-cm or more.
1000
1200
1400

Cancer
Spectroscopic Lens
No Cancer
Flexible Cystoscope

Prototype-1 instrumentation for
in-vitro imaging of human samples
Absorption spectra of
main tissue fluorophores
We use longer wavelengths for
selective excitation of Porphyrins
Excitation
wavelengths
Illumination wavelengths
for light scattering imaging
600 700 800 900
Imaging spectral range

Is What You See Cancer?
What stage is it?

Is All Cancer Gone?
RESECTION for CURE
(In ⅓ of cases, the answer is NO)

Spectroscopic images of a bladder
tissue specimen containing cancer
C-P LSI NIR FI @ 532 nm NIR FI @ 633 nm
Ratio Images Direct Images
NIR FI @ 633 /
NIR FI @ 532
C-P LSI @ 1000
NIR FI @ 532
H&E stain

SPDI imaging using a cystoscope
and an animal tissue model
Images of a 2.5-cm thick breast chicken tissue containing
other tissue components located below its surface
690 nm illumination
direct image
820 nm illumination
direct image
970 & 820 nm illumination
SPDI image
Tendon (≈2 mm thick)
located 5 mm
below the surface
Fat lesion (≈2 mm thick)
located 10 mm
below the surface

We are working on prototype-3
system with dual-image capabilities
• System under
construction displays
simultaneously
conventional color
images and cancer
enhancing NIR images
• The system in its final
form will include the
subsurface imaging
module
• This system will be
readily adaptable to
any type of endoscope

Figure 1
Breast Cancer
NIR autofluorescence image under
a) 532 nm excitation and
b) 632,8 nm excitation of a 4-cm X
3-cm human breast tissue, ≈6-
mm thick.
c) A contrast-enhanced H&E
stained paraffin section of the
same specimen with tumor
location indicated by an arrow.
d) Intensity profiles of images
(a) and (b) along a vertical line
passing through the middle of
the tumor.

Ex Vivo Results
TCC 25/25 Accurate 100%
All Tumors
80/81 Accurate

Delivered to Date
1 Grant 3 Papers Required Patents
Ex-Vivo
80/81 Tissues Accurately Analyzed
In-Vivo
NIR Tissue Analysis Prior to Clinical Testing
Beam Splitter to show Tumor/Tissue on TV Monitor
(200-400 wvl)
NIR on TV Monitor (600-1000 wvl)

“TABLETOP”
Proton Radiotherapy System
We will bring the pinpoint
accuracy and efficacy of proton
radiotherapy to every cancer
patient

THEME C: Cancer Therapy Technology
Compact Proton Accelerator
MD Anderson Proton Beam Facility ($200M)
Built CPA to fit in Linac Vault ($10M)

“Proton therapy is the most precise form of
advanced radiation treatment available for certain
cancers and other diseases” -- Jerry D. Slater, MD
Chair, Department of Radiation Medicine
Loma Linda University
“The device would revolutionize radiation oncology”
NIH Summary Statement
“The only serious discussion concerning proton
therapy implementation is cost, not rationale”
Suit 2002

PRS TEAM
LLNL:
Dennis Matthews, PhD -Director, Center for Biotechnology,
Biophysical Sciences and Bioengineering
George Caporaso, PhD - Program Leader for Beam Research
Program
UCDHS:
Ralph deVere White, MD –Director, UC Davis Cancer Center,
Chairman, Department of Urology
Srinivasan Vijayakumar, MD –Chairman, Radiation Oncology
James Purdy, Ph.D – Chief Physicist, Radiation Oncology

Equipment Manufacturer
Perspective
• Clinic-sized proton therapy system sales
projections in the US at target price point:
Penetration rate
Sales in Billions
Sales price
(bil)
1%
2%
5%
10%
15%
20%
$ 5
$ 93
$186
$ 465
$ 930
$1,395
$1,860
$ 10
$ 186
$372
$ 930
$1,860
$2,790
$3,720
$ 15
$ 279
$558
$1,395
$2,790
$4,185
$5,580
Assumptions: Rad Onc Clinics in the US: 1,860
LINACS in the North America: 3900 (per Varian)
No analysis of consumables, service revenue or foreign markets

The Compact Proton Radiotherapy System Concept*
• Pencil beam is mechanically scanned in x and y
• Flexible dose delivery via pulse-to-pulse variable
energy and intensity
• Energy range 70 - 250 MeV
• Dose range 0 - 20 Gy/sec/beam cross section area (cm 2 )at
the Bragg peak
• Multiple patient delivery configurations possible to
accommodate available space
Vertical option
Isocentric option
* Patent pending
Horizontal option
with in-situ CT scan

While risks remain, we believe a compact
proton accelerator based on DWA
technology is feasible
• Multiple viable architectures exist
• Two promising switch candidates are being developed
• There are multiple dielectric material sources
• Pulse format consistent with treatment needs
• Pencil beam scanning can be achieved without bending magnets
• Beam dynamics appears straightforward
• Novel compact proton source can deliver high peak current
• In continuing development we must demonstrate
– HGI performance for large lengths (≈ 6-8 cm)
– Multiple pulse operation of source with acceptable beam quality
– Integrated system performance

John M. Boone, Ph.D. – Principal Investigator
Karen K. Lindfors, M.D.
Thomas R. Nelson, Ph.D.

Mammography: the superposition problem
mammography

CT: the superposition problem solved
breast CT

Breast CT Prototype “Albion” at the University of California, Da

The UC Davis Breast Tomography Project

296
pectoralis
Healthy Volunteer

mlo
cc
316
implant patient with cancer indicated with arrows

Contrast Enhanced
Breast CT (injected
iodine contrast agent
shows additional cancer)

Clinical Studies Underway
Phase I clinical trial: 10 healthy volunteers
Phase II clinical trial:
190 BIRADS 4 and 5 women (going to be biopsied)
Phase II clinical trial:
Iodine injection 3 BIRADS 5 women
10/10
26/190
3/3
Funded other developments
PET / CT dedicated breast imaging system
Ultrasound / CT dedicated breast imaging system