Optical imaging for breast cancer prescreening

Figures & data

Table 1 Conventional breast cancer prescreening/screening and emerging imaging modalities

	Modality	Physics	Application	Advantages	Disadvantages	Sensitivity	Specificity
Examinations	SBE	Self-physical examination for detecting breast lesions	Prescreening	Increases public awareness Can be used on high-risk populations Easy technique that can be performed at home	No effect on mortality of breast cancer^Citation30 High rates of false positives and overdiagnosis^Citation31	12%–14%^Citation32	–
	CBE	Clinical breast examination for detecting breast lesions	Prescreening	Reduced breast cancer mortality	No randomized controlled trails have been conducted of CBE in women not receiving other forms of screening^Citation30	57.14%^Citation34	97.11%^Citation34
				Can detect breast cancer missed by mammography (sometimes) May be effective in reducing mortality in women	Increased false-positive results^Citation32 Does not permit one to determine malignancy with assurance^Citation33 High rates of false positives and overdiagnosis^Citation31	40%–69%^Citation32	86%–99%^Citation32
Conventional imaging Emerging modalities	X-ray mammography (structural imaging)	High energy X-rays travel in a straight path and are attenuated by interaction with tissue	Screening (gold standard), diagnostic, prognostic	High specificity and sensitivity to detecting cancers Portable device	10% of false-positive cases Poor contrast compared to CT or MRI	68.6% (in 40–44 year olds) 83.3% (in 80–89 year olds)^Citation35	91.4%–94.4% (w/hormone replacement therapy)^Citation35
				Fast imaging time (approximately <1 minute) Good resolution (∼mm) More accuracy in dense breasts when using digital mammography	Uses ionizing radiation Less sensitive in radiographically dense breasts^Citation35
	Ultrasound (structural imaging)	Acoustic waves (mechanical) are introduced into the body and are reflected back toward a receiver	Screening, diagnostic, prognostic	High diagnostic utility among women with dense breasts^Citation30 Portable device Fast imaging time (approximately <1 minute) Nonionizing (safe)	High false-positive rates^Citation30 Poor contrast Poor resolution (∼cm)	Increases from 36% to 95% with Doppler^Citation36	Decreases from 86% to 79% with Doppler^Citation36
	CT (structural)	3D arrays of X-rays travel in a straight path and are attenuated by interaction with tissue	Screening, diagnostic, prognostic	Good resolution (∼mm) Poor contrast Fast imaging time (approximately <1 minute)	Non-portable device Expensive device	–	–
	MRI (structural)	RF signal is used to align water molecules to a changing magnetic field where the resultant RF signal is collected	Screening, diagnostic, prognostic	Sensitivity is nearly 100%^Citation12,Citation37 Can better detect intraductal spread of cancer^Citation12	Specificity values vary^Citation12 and are poor^Citation37 MRI-guided biopsies are difficult and require compatible equipment^Citation12	88.1%^Citation38	67.7%^Citation38
				Good technique for post- chemotherapy imaging^Citation12 Excellent resolution (<mm) Nonionizing radiation	Only the lateral side of the breast is visible^Citation12 Not portable Slow imaging time (approximately over 20 minutes) Expensive device Good contrast
	PET (nuclear) – functional imaging	High-energy radioactive isotopes create two gamma rays that travel in opposite directions toward detectors	Screening, diagnostic, prognostic	Good contrast Functional information	Ionizing radiation Poor resolution (∼cm) Not portable Expensive device Slow imaging time (approximately over 20 minutes)	96%^Citation39	77%^Citation39
	Scintimammography – (functional imaging)	Uses nonspecific radionuclides to identify malignant lesions	Diagnostic	Good contrast Functional information	Ionizing radiation Not portable Slow imaging time High false positives^Citation40,Citation41 Low sensitivity for small cancers (<1–1.5 cm) and ductal carcinoma in situ^Citation42	93%^Citation43	87%^Citation43
	Thermography (functional imaging)	Identifies vascular and temperature changes	Screening, diagnostic	Noninvasive Non-radiative Less imaging time Promise for dense breasts^Citation44	Easily affected by temperature Large breasts are poorly imaged High false positives and false negatives^Citation26	97%^Citation45	14%^Citation45
	Electrical impedance tomography (functional and structural)	Measures local dielectric properties of cancer cells, including electrical conductance and capacitance	Diagnostic, but works better for screening^Citation46	Noninvasive, non-radiative, and risk free Works well with dense breasts Relatively inexpensive^Citation46^–^Citation48 Scans in approximately 15 minutes	High false-positive rates^Citation49 Poor spatial resolution than CT or MRI	72.2%^Citation50 38%^Citation46	67%^Citation50 95%^Citation46
	Microwave imaging (functional)	Employs microwave or millimeter waves to image dielectric bodies	Diagnostic	Noninvasive Non-radiative	Poor resolution at higher depth^Citation48 Low contrast in fibroglandular tissues	–	–
	Optical imaging (functional)	Employs near-infrared light (650–900 nm) to measure differences in absorption and scattering coefficients across different tissues	Screening, diagnostic, prognostic	Noninvasive Non-radiative Relatively inexpensive and portable Low imaging time (<1 minute) Good contrast (since functional information)	Highly scattered signal limits its depth imaging Limited spatial resolution when optical fibers are used	–	–

Abbreviations: SBE, self-breast examination; CBE, clinical breast examination; CT, computerized tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; RF, radio frequency.

Figure 1 Spectrum of absorption from 400 nm to 1,000 nm.

Notes: The biological optical imaging window allows deeper penetration of light from the wavelengths of around 650–900 nm due to minimal absorption by the tissue components, HbO, Hb, and H₂O in this wavelength range. Adapted by permission from Macmillan Publisher Ltd: Weissleder R. A clearer vision for in vivo imaging. Nat Biotechnol. 2001;19(4):316–317, Copyright ©2001.⁵³
Abbreviation: Hb, hemoglobin.

Figure 2 Different hand-held probes developed for early detection of breast cancer, showing their source–detector layouts and the actual device.

Note: The source-detector configuration and the actual device are shown for each of the devices (A-I) in Table 2. (A) Adapted from Tromberg BJ. Optical scanning and breast cancer. Acad Radiol. 2005;12(8):923–924, with permission from Elsevier.⁶² (B) ©2005 IEEE. Reprinted, with permission, from No KS, Chou PH. Mini-FDPM and heterodyne mini-FDPM: handheld non-invasive breast cancer detectors based on frequency-domain photon migration. IEEE Trans Circ Syst I Reg Papers. 2005;52(12):2672–2685.⁷⁷ (C) Adapted from Chance B, Nioka S, Zhang J, et al. Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study. Acad Radiol. 2005;12(8):925–933, with permission from Elsevier.¹³⁸ (D) Adapted with permission from Chance B, Zhao Z, Wen S, Chen Y. Simple ac circuit for breast cancer detection and object detection. Rev Sci Instrum. 2006;77:064301. Copyright ©2006, AIP Publishing LLC.⁵⁹ (E) Adapted with permission from Xu RX, Qiang B, Mao JJ, Povoski SP. Development of a handheld near-infrared imager for dynamic characterization of in vivo biological tissue systems. Appl Opt. 2007;46(30):7442–7451.⁵⁹ (F) Adapted from Zhu Q, Huang M, Chen N, et al. Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions: initial clinical results of 19 cases. Neoplasia. 2003;5(5):379–388, with permission from Elsevier.¹¹⁴ (G) Adapted from Flexman ML, Kim HK, Stoll R, Khalil MA, Fong CJ, Heilscher AH. A wireless handheld probe with spectrally constrained evolution strategies for diffuse optical imaging of tissue. Rev Sci Instrum. 2012;83:033108. Copyright ©2012, AIP Publishing LLC.¹¹⁵
Abbreviation: CMOS, complementary metal oxide semiconductor.

Table 2 Optical imaging devices developed for prescreening or early-stage breast cancer imaging

Number	Reference	Modality	Measurement technique	Source type	Detector type	Size	Clinical application(s)
1	Tromberg et al^Citation64	DOS	FD (300 kHz–1 GHz)	Laser diodes (10–30 mW) (674 nm, 811 nm, 849 nm, 956 nm)	APD	–	Compare optical properties of normal and benign lesion-containing breast tissue
2	No et al^Citation79	DOS	FD (10 MHz–1 GHz)	Eight laser diodes (50 mW) (783 nm)	APD	–	Noninvasive breast cancer detection based on frequency-domain photon migration
3	Nioka and Chance^Citation80	DOS	CW	Light-emitting diodes (10–15 mA) (760 nm, 805 nm, 850 nm)	Eight silicon diode detectors	∼9 cm diameter	Determine sensitivity and specificity of detecting breast cancer in 116 human subjects. Obtained 93% specificity and 96% sensitivity
4	Chance et al^Citation59	DOS	CW	Two light-emitting diodes (20 mA) (800 nm) – out of phase sources	One silicon diode detector	9.3×6.5×3 cm^3 (similar in size to glucose meter)	Detection and 2D localization of breast cancer lesion in a human subject
5	Cheng et al^Citation83	DOS	CW	Laser diodes (0.15 W/cm^2) (690 nm, 830 nm)	PMT	5.5×5.5×10.2 cm^3	Determine sensitivity and specificity of detecting ductal carcinoma in 50 human subjects. Obtained 92% diagnosed sensitivity and 67% diagnosed specificity
6	Zhu et al^Citation114	DOT and US	FD (200 MHz)	Eight dual-wavelength laser diodes (690 nm, 780 nm, 830 nm)	APD	–	Image benign and malignant lesions at early stage in breast tissue
7	Flexman et al^Citation115	DOS (wireless)	CW	Laser diodes (10 mW) (780 nm, 808 nm, 850 nm, 904 nm)	Two silicon photodiodes	11.5×16×2.5 cm^3	Liquid phantom studies to demonstrate measurement of HbO, HbR, and scattering in tissues. In vivo data not available
8	Xu et al^Citation60	DOI (P-Scan Imager, Vioptix Inc.)	CW	Eight dual-wavelength laser diodes (690 nm, 830 nm)	Eight silicon photodiodes	5.5×5.5×10.2 cm^3	In vivo human tissue studies for dynamic characterization by reconstructing absorption coefficients. In vivo breast imaging studies are not available
9	Labib et al^Citation116	Breast illumination	CW	617 nm visible red light	Naked eye	–	Imaged 310 women (43.6±12.4 years) for breast screening. Obtained 73.7% specificity, 93% sensitivity, 91.4% PPV, 77.8% NPV, and 88.2% accuracy. Detects lesions 15 mm and above
10	Rodriguez et al^Citation117	DOI (NIROS)	CW	Light-emitting diode (710 nm)	CMOS camera	5×7×15 cm^3	In vivo breast imaging studies using tumor- like targets. No data from breast cancer subjects

Abbreviations: APD, avalanche photodiode; CMOS, complementary metal oxide semiconductor; CW, continuous wave; DOI, diffuse optical imaging; DOS, diffuse optical spectroscopy; DOT, diffuse optical tomography; FD, frequency domain; NIROS, near-infrared optical scanner; PMT, photon multiplier tube; PPV, Positive predictive value; NPV, Negative predictive value; US, ultrasound.

Figure 3 Setup for breast imaging studies consisting of the breast tissue placed in between two transparent plates.

Notes: A detector is placed above the top plate, the source is placed beneath the bottom plate, and a target is placed beneath the breast tissue and above the bottom plate.
Abbreviation: NIR, near-infrared.

Figure 4 Transmitted NIR optical images of the left breast from subject #1 that were captured at a constant pressure applied on the breast (in all images).

Notes: (A) NIR image was captured without pressure and without target. (B) NIR image was captured without pressure and with the target placed at the location indicated by the black hollow circle at 12 o’clock. (C) Post-processed NIR image after co-registering, subtracting, and masking. The black hollow circle in (B and C) depicts the 2D location of the target at 12 o’clock position in the intramammary fold of the left breast.
Abbreviation: NIR, near-infrared.

Figure 5 Transmitted NIR optical images of the left breast from subject #2 that were captured at a constant pressure applied on the breast (in all images).

Notes: (A) NIR image was captured with applied pressure and without target. (B) NIR image was captured with applied pressure and with the target placed at the location indicated by the hollow black circle at 6 o’clock. (C) Post-processed NIR image after co-registering, subtracting, and masking. The black hollow circle in (B) and (C) depicts the 2D location of the target at 6 o’clock position in the intramammary fold of the left breast.
Abbreviation: NIR, near-infrared.

Al-ForheidiMAl-MansourMMIbrahimEMBreast cancer screening: a review of benefits and harms and recommendations for developing and low-income countriesMed Oncol201330247123420062

 PubMed Web of Science ®Google Scholar

MillerABBainesCJThe role of clinical breast examination and breast self-examinationPreventative Med2011533118120

 Web of Science ®Google Scholar

MaIDueckAGrayRClinical and self breast examination remain important in the ear of modern screeningAnn Surg Oncol20121951484149022160521

 PubMed Web of Science ®Google Scholar

RatanachaikanontTClinical breast examination and its relevance to diagnosis of palpable breast lesionJ Med Assoc Thai200588450550716146255

 PubMedGoogle Scholar

KhaliliAFShahnaziMBreast cancer screening (breast self-examination, clinical breast exam, and mammography) in women referred to health centers in Tabriz, IranIndian J Med Sci201064414916222718010

 PubMedGoogle Scholar

CarneyPAMigliorettiDLYankaskasBCIndividual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammographyAnn Intern Med2003138316817512558355

 PubMed Web of Science ®Google Scholar

MoonWKImGJNohDYHanMCNonpalpable breast lesions: evaluation with power Doppler US and a microbubble contrast agent-initial experienceRadiology2000217124024611012451

 PubMed Web of Science ®Google Scholar

NoverABJagtapSAnjumWModern breast cancer detection: a technological reviewInt J Biomed Imaging20092009114

 Google Scholar

SaslowDBoetesCBurkeWfor the American Cancer Society Breast Cancer Advisory GroupAmerican Cancer Society guidelines for breast screening with MRI as an adjunct to mammographyCA Cancer J Clin200757758917392385

 PubMed Web of Science ®Google Scholar

BluemkeDAGatsonisCAChenMHMagnetic resonance imaging of the breast prior to biopsyJ Am Med Assoc20042922227352742

 PubMed Web of Science ®Google Scholar

LindPIgercIBeyerTReinprechtPHauseggerKAdvantages and limitations of FDG PET in the follow-up of breast cancerEur J Nucl Med Mol Imaging200431Suppl 1S125S13415085295

 PubMedGoogle Scholar

LibermanMSampalisFMulderDSSampalisJSBreast cancer diagnosis by scintimammography: a meta-analysis and review of the literatureBreast Cancer Res Treat200380111512612889605

 PubMed Web of Science ®Google Scholar

KlausAJKlingensmithWC3rdParkerSHStavrosATSutherlandJDAldreteKDComparative value of 99mTc-sestamibi scintimammography and sonography in the diagnostic workup of breast massesAJR Am J Roentgenol200017461779178310845522

 PubMed Web of Science ®Google Scholar

KhalkhaliIIttiEFunctional breast imaging using the single photon techniqueNucl Med Commun200223760961112089481

 PubMed Web of Science ®Google Scholar

SampalisFSDenisRPicardDInternational prospective evaluation of scintimammography with t99mechnetium sestamibiAm J Surg2001182439940311720679

 PubMed Web of Science ®Google Scholar

AroraNMartinsDRuggerioDEffectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancerAm J Surg2008196452352618809055

 PubMed Web of Science ®Google Scholar

SternsEECurtisACMillerSHancockJRThermography in breast diagnosisCancer19825023233257083138

 PubMed Web of Science ®Google Scholar

PariskyYRSardiAHammREfficacy of computerized infrared imaging analysis to evaluate mammographically suspicious lesionsAJR Am J Roentgenol2003180126326912490517

 PubMed Web of Science ®Google Scholar

NgEYKFokSCPehYCNgFCSimLSJComputerized detection of breast cancer with artificial intelligence and thermogramsJ Med Eng Technol200226415215712396330

 PubMedGoogle Scholar

BrownBHElectrical impedance tomography (EIT): a reviewJ Med Eng Technol20032739710812775455

 PubMedGoogle Scholar

MartínGMartínRBrievaMJSantamaríaLElectrical impedance scanning in breast cancer imaging: correlation with mammographic and histologic diagnosticEur Radiol20021261471147812042956

 PubMed Web of Science ®Google Scholar

MelloulMPazAOhanaGDouble-phase 99mTc-sestamibi scintimammography and trans-scan in diagnosing breast cancerJ Nucl Med199940337638010086698

 PubMed Web of Science ®Google Scholar

WeisslederRA clearer vision for in vivo imagingNat Biotechnol200119431631711283581

 PubMed Web of Science ®Google Scholar

TrombergBJOptical scanning and breast cancerAcad Radiol200512892392416087089

 PubMed Web of Science ®Google Scholar

NoKSChouPHMini-FDPM and heterodyne mini-FDPM: handheld non-invasive breast cancer detectors based on frequency-domain photon migrationIEEE Trans Circ Syst I Reg Papers2005521226722685

 Web of Science ®Google Scholar

ChanceBNiokaSZhangJBreast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site studyAcad Radiol200512892593316023383

 PubMed Web of Science ®Google Scholar

ChanceBZhaoZWenSChenYSimple ac circuit for breast cancer detection and object detectionRev Sci Instrum200677064301

 Web of Science ®Google Scholar

ZhuQHuangMChenNUltrasound-guided optical tomographic imaging of malignant and benign breast lesions: initial clinical results of 19 casesNeoplasia20035537938814670175

 PubMed Web of Science ®Google Scholar

FlexmanMLKimHKStollRKhalilMAFongCJHeilscherAHA wireless handheld probe with spectrally constrained evolution strategies for diffuse optical imaging of tissueRev Sci Instrum20128303310822462907

 PubMed Web of Science ®Google Scholar

TrombergBJCoquozOFishkinJBNon-invasive measurements of breast tissue optical properties using frequency-domain photon migrationPhilos Trans R Soc Lond B Biol Sci19973526616689232853

 PubMed Web of Science ®Google Scholar

NoKSXieQKwongRIn vivo breast cancer measurement with a handheld laser breast scannerProceedings of the 50th IEEE International Midwest Symposium on Circuits and SystemsAugust 5–8 2007Montreal, Quebec, Canada200714

 Google Scholar

NiokaSChanceBNIR spectroscopic detection of breast cancerTechnol Cancer Res Treat20054549751216173821

 PubMed Web of Science ®Google Scholar

ChengXMaoJBushRKopansDBMooreRHChorltonMBreast cancer detection by mapping hemoglobin concentration and oxygen saturationAppl Opt2003426412642114649285

 PubMed Web of Science ®Google Scholar

XuRXQiangBMaoJJPovoskiSPDevelopment of a handheld near-infrared imager for dynamic characterization of in vivo biological tissue systemsAppl Opt200746307442745117952180

 PubMed Web of Science ®Google Scholar

LabibNAGhobashiMMMoneerMMHelalMHAbdalgaleelSAEvaluation of BreastLight as a tool for early detection of breast lesions among females attending National Cancer Institute, Cairo UniversityAsian Pac J Cancer Prev20131884647465024083718

 PubMedGoogle Scholar

RodriguezSKaliadaHGabrielleCJungY-JGodavartyAIn-vivo breast imaging using an ultra-portable hand-held near-infrared optical scanner (NIROS)OSA J Biomed OptApril 26–30, 2014Miami, FL2014BM3A.66

 Google Scholar