(12) United States Patent Bambot et a].

US008644912B2

US 8,644,912 B2 Feb. 4, 2014

(10) Patent N0.: (45) Date of Patent:

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SYSTEM AND METHOD FOR DETERMINING TISSUE CHARACTERISTICS

Inventors: Shabbir Bambot, Suwanee, GA (US); Mark L. Faupel, Alpharetta, GA (US); Anant AgraWal, Atlanta, GA (US); Keith D. Ignotz, Duluth, GA (US); Andrew Fordham, Sugar Hill, GA (US)

SpectRx, Inc., Norcross, GA (US) Subject to any disclaimer, the term of this patent is extended or adjusted under 35 USC 154(b) by 0 days.

Appl. No.: 13/214,638

Assignee: Notice:

Filed: Aug. 22, 2011

Prior Publication Data

US 2011/0306887 A1 Dec. 15,2011

Related US. Application Data

Continuation of application No. 12/099,876, ?led on Apr. 9, 2008, noW abandoned, and a continuation of application No. 10/647,222, ?led on Aug. 26, 2003, noW abandoned, and a continuation-in-part of application No. 10/611,917, ?led on Jul. 3, 2003, noW Pat. No. 7,006,220, and a continuation-in-part of application No. 10/603,597, ?led on Jun. 26, 2003, noW Pat. No. 6,975,899, and a continuation-in-part of application No. 10/446,857, ?led on May 29, 2003, noW Pat. No. 6,870,620, and a continuation-in-part of application No. 10/337,687, ?led on Jan. 8, 2003, noW abandoned, and a continuation-in-part of application No. PCT/US02/06350, ?led on Mar. 1, 2002, and a continuation of application No. 09/786,781, ?led on Mar. 9, 2001, noW abandoned, application No. 13/214,638, Which is a continuation of application No. 09/700,538, ?led on Nov. 16, 2000, noW Pat. No. 6,590,651, and a division of application No. 09/533,817, ?led on Mar. 24, 2000, noW Pat. No. 6,577,391, and a continuation of application No. 09/434,518, ?led on Nov. 5, 1999, noW abandoned, Which is a continuation-in-part of application No. PCT/US99/20646, ?led on Sep. 10, 1999, and a continuation-in-part of application No. PCT/US99/10947, ?led on May 19, 1999.

(60) Provisional application No. 60/272,458, ?led on Mar. 2, 2001, provisional application No. 60/126,056, ?led on Mar. 23, 1999.

Int. Cl. A61B 6/00 US. Cl. USPC .......... .. 600/476; 600/407; 600/473; 600/478 Field of Classi?cation Search USPC ................................ .. 600/407, 473, 476, 478 See application ?le for complete search history.

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(56) References Cited

U.S. PATENT DOCUMENTS

4,534,360 A * 6,364,829 B1 6,571,118 B1

8/1985 Williams .................... .. 600/473

4/2002 Fulghum 5/2003 UtZinger et al.

FOREIGN PATENT DOCUMENTS

W0 WO 00/15101 3/2000 OTHER PUBLICATIONS

Shabbir B. Bambot et al., “Sensing oxygen through skin using a red diode laser and ?uorescence liftetimes”, Biosens and Bioelectronics, vol. 10, Nov. 6/7, pp. 643-652, 1995. Kevin T. Shoemacher et al., “Ultraviolet Laser-Induced Fluorescence of Colonic Tissues: Basic Biology and Diagnostic Potential”, Laser in Surgery Medicine, vol. 12, pp. 63-78, 1992.

(Continued) Primary Examiner * Peter Luong

(74) Attorney, Agent, or Firm * Altera LaW Group, LLC

(57) ABSTRACT An apparatus to interrogate, receive, and analyze full emis sion spectra for at least one ?uorescence excitation Wave length and for at least one re?ectance measurement to deter mine tissue characteristics. The apparatus includes a base unit having illumination, detection and control sub-units, the illu mination sub-unit providing illumination optical energy for illuminating a target tissue and the detection sub-unit detect ing tissue characteristics of a target tissue, a separate tissue interface unit, and a pathWay coupling the base unit and the tissue interface unit. The system and apparatus may also include a tube for maintaining the distance between the tissue and units and for surrounding the tissue to prevent patient movement from being transmitted to the tissue.

25 Claims, 24 Drawing Sheets

80a

US 8,644,912 B2 Page 2

(56) References Cited

OTHER PUBLICATIONS Charles E. Alpers et al., “The Prevalance of Carcinoma in Situ in Normal and Cancer Associated Breasts”, Human Pathology, vol. 16, No. 8, pp796-807, Aug. 1985.

Danely Slaughter et al., Field CanceriZation in Oral Strati?ed Squamour Epithelium: Clinical Implication of Multicentric Origin Cancer, vol. 6, No. 4, pp. 963-968, 1953. Cancer Diagnostics: The World Markets, Clinical Reports, PJB Pub lications, p. 72, 1997.

* cited by examiner

US. Patent Feb. 4, 2014 Sheet 1 m4 US 8,644,912 B2

44

78a

80

:1

'74

//

FIG. 1A

80a

FIG. 2

US. Patent Feb. 4, 2014 Sheet 2 m4 US 8,644,912 B2

SUB-UNIT DETECTION

2O L-___________________________f

ILLUMINATION SOURCE

ILLUMINATION SUB-UNIT

ELECTRO OPTIC

FIG. 1B

US. Patent Feb. 4, 2014 Sheet 3 m4 US 8,644,912 B2

72b

FIG. 1C

US. Patent Feb. 4, 2014 Sheet 4 m4 US 8,644,912 B2

# Measurement Excitation Collection SpeC’UO— Meas. graph time center A secs

Flourescence 350 nm (10 nm BP) 385 nm LP (66 385) 450nm 2 Flourescence 400 nm (10 nm BF’) 420 nm LP (GG 485) 500nrn 2 Flourescenee 460 nm (10 nm BP) 495 nm LP ((56 495) 560nm 4 Reflectance OD1.5 ND filter 300-700 nm DD (56 26) 500nm 0.2

BPzbandpass LP=Long-pass

FIG. 6

US. Patent Feb. 4, 2014 Sheet 5 m4 US 8,644,912 B2

a 3 2

FIG. 4

12345678

FIG. 5

US. Patent Feb. 4, 2014 Sheet 6 m4 US 8,644,912 B2

170 177 K

119

182

i182 &12O

FIG. 7A

US. Patent Feb. 4, 2014 Sheet 7 m4 US 8,644,912 B2

170 199 \—l w SYSTEM '

POWER INTERFACE I MONITOR AND I

re?ected/ 1 78b CONTROLLER

emitted ' 1I78 178a 1I87 I light T“ — F FVIDEO

% fig) VIDEO CONTROLLER 1% ' I 173a 1730 175 .

159 I57 j I58 1I58a W T m _ r 4 ‘CAMERA I '

,lj 41w CAMERA CONTROLLER I 100 I 156 155 (130 I

Z ' m- LIGHT GUIDE 4 I

light M - —~ — -

‘1313 131 173b,173d I

M7721 I

k LITTb

K1770 183

IMAGE J r __________ L1

DOCKING I I STATION I I REDCEORDING I MONITOR I

182 182a VICE I I

120) (1823 ““““ FIG. 7B

US. Patent Feb. 4, 2014 Sheet 8 m4 US 8,644,912 B2

177 177

[120

POWER PROCESSOR SUPPLY

\ L 190 191 182

ILLUMINATION ILLUMINATION VID’EO SOURCE SOURCE OUT

CONTROLLER

\I 32 \132A

DOCKINC UNIT

FIG. 8A

US. Patent Feb. 4, 2014 Sheet 9 m4 US 8,644,912 B2

1953

503

501 DATA ) TRANSMITTER j |NTERFACE / APERTURE/ UNIT

FILTER MOTOR CONTROLLER

504 502 SHUTTER ) llgll'sEiiigEE /

CONTROLLER UNIT

505

ANALOG ) INTERFACE /'

UNIT

FIG. 8B

US. Patent Feb. 4 2014 Sheet 11 0f 24

FIG. 10

US. Patent Feb. 4, 2014 Sheet 12 0f 24 US 8,644,912 B2

[186 ’\

(172 ( 130

u g D O i

1 74

170

FIG. 11

US. Patent Feb. 4, 2014 Sheet 13 m4 US 8,644,912 B2

199

r174

K /187

170

FIG. 12

US. Patent Feb. 4, 2014 Sheet 14 0f 24 US 8,644,912 B2

210

205

200 <

FIG. 13

US. Patent Feb. 4, 2014 Sheet 15 m4 US 8,644,912 B2

210————

200

FIG.14

US. Patent Feb. 4, 2014 Sheet 16 m4 US 8,644,912 B2

-1 Order Spectra 0th ?irx<+1 Order Spectra

CCD Camera ——> + / 0c

COG)

(DOC)

CDOCD

CDOQ

(:06

CO6

|——+ @OQ Virtual Area of 0C Cervix as

projected on CCD

FIG. 15

US. Patent Feb. 4, 2014 Sheet 17 m4 US 8,644,912 B2

CCEQWay [ Virtual Area of Cervix

210\ /21O Cb <50

<30 06

C00 COG

(I) <:> O CID

CID O 0CD (Dd

CD Cl) (:3 CD

CD06 (DOC;

O0 0CD

O0 ——-——————> 0O

FIG. 16

US. Patent Feb. 4, 2014 Sheet 18 m4 US 8,644,912 B2

CCD Array Virtual Area of Cervix

210\

FIG. 17