View source for Diffuse optical mammography

{{main|Breast imaging}}
{{Infobox diagnostic
| name            = Diffuse optical mammography
| image           = Example of tissue composition maps. - Fig.2.jpg
| alt             = 
| caption         = Example of breast constituents' concentrations maps through optical mammography (right cranio-caudal view). The blue arrow points to the lesion. Hb stands for deoxy-hemoglobin, HbO<sub>2</sub> for oxy-hemoglobin, tHb for total hemoglobin.<ref name="Taroni-2017" />
| image_size    =  400px
| purpose         =investigation of the breast composition through spectral analysis
| test of         =
| based on        =
| synonyms        = 
| reference_range =
| calculator      = 
| DiseasesDB      = <!--{{DiseasesDB2|numeric_id}}-->
| ICD10           = <!--{{ICD10|Group|Major|minor|LinkGroup|LinkMajor}} or {{ICD10PCS|code|char1/char2/char3/char4}}-->
| ICD9            = 
}}
'''Diffuse optical mammography''', or simply '''optical mammography''', is an emerging [[Breast imaging|imaging technique]] that enables the investigation of the [[breast]] composition through [[Near-infrared spectroscopy|spectral analysis]]. It combines in a single non-invasive tool the capability to implement [[breast cancer]] risk assessment,<ref name="Taroni-2010">{{cite journal |last1=Taroni |first1=Paola |last2=Pifferi |first2=Antonio |last3=Quarto |first3=Giovanna |last4=Spinelli |first4=Lorenzo |last5=Torricelli |first5=Alessandro |last6=Abbate |first6=Francesca |last7=Villa |first7=Anna |last8=Balestreri |first8=Nicola |last9=Menna |first9=Simona |last10=Cassano |first10=Enrico |last11=Cubeddu |first11=Rinaldo |title=Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy |journal=Journal of Biomedical Optics |date=2010 |volume=15 |issue=6 |pages=060501–060501–3 |doi=10.1117/1.3506043|pmid=21198142 |bibcode=2010JBO....15f0501T |doi-access=free }}</ref> lesion characterization,<ref name="Quarto-2014">{{cite journal |last1=Quarto |first1=Giovanna |last2=Spinelli |first2=Lorenzo |last3=Pifferi |first3=Antonio |last4=Torricelli |first4=Alessandro |last5=Cubeddu |first5=Rinaldo |last6=Abbate |first6=Francesca |last7=Balestreri |first7=Nicola |last8=Menna |first8=Simona |last9=Cassano |first9=Enrico |last10=Taroni |first10=Paola |title=Estimate of tissue composition in malignant and benign breast lesions by time-domain optical mammography |journal=Biomedical Optics Express |date=18 September 2014 |volume=5 |issue=10 |pages=3684–3698 |doi=10.1364/BOE.5.003684|pmid=25360382 |pmc=4206334 }}</ref> therapy monitoring<ref name="jiang-2009">{{cite journal |last1=Jiang |first1=Shudong |last2=Pogue |first2=Brian W. |last3=Carpenter |first3=Colin M. |last4=Poplack |first4=Steven P. |last5=Wells |first5=Wendy A. |last6=Kogel |first6=Christine A. |last7=Forero |first7=Jorge A. |last8=Muffly |first8=Lori S. |last9=Schwartz |first9=Gary N. |last10=Paulsen |first10=Keith D. |last11=Kaufman |first11=Peter A. |title=Evaluation of Breast Tumor Response to Neoadjuvant Chemotherapy with Tomographic Diffuse Optical Spectroscopy: Case Studies of Tumor Region-of-Interest Changes |journal=Radiology |date=August 2009 |volume=252 |issue=2 |pages=551–560 | pmc=2753781|  doi=10.1148/radiol.2522081202|pmid=19508985 |doi-access=free }}</ref> and prediction of therapy outcome.<ref name="Cerussi-2007">{{cite journal |last1=Cerussi |first1=A. |last2=Hsiang |first2=D. |last3=Shah |first3=N. |last4=Mehta |first4=R. |last5=Durkin |first5=A. |last6=Butler |first6=J. |last7=Tromberg |first7=B. J. |title=Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy |journal=Proceedings of the National Academy of Sciences |date=28 February 2007 |volume=104 |issue=10 |pages=4014–4019 |doi=10.1073/pnas.0611058104|pmid=17360469 |pmc=1805697 |bibcode=2007PNAS..104.4014C |doi-access=free }}</ref> It is an application of [[Diffuse optical imaging|diffuse optics]], which studies light propagation in strongly diffusive media, such as biological tissues, working in the [[Light|red]] and [[Infrared|near-infrared]] spectral range, between 600 and 1100&nbsp;nm.<ref name="Martelli-2009">{{cite book |last1=Martelli |first1=Fabrizio |last2=Del Bianco |first2=Samuele |last3=Ismaelli |first3=Andrea |last4=Zaccanti |first4=Giovanni |title=Light propagation through biological tissue and other diffusive media : theory, solutions, and software |year=2010 |publisher=SPIE |isbn=9780819476586}}</ref>

== Comparison with conventional imaging techniques ==
Currently, the most common [[Breast imaging|breast imaging techniques]] are [[Mammography|X-ray mammography]], [[Breast ultrasound|ultrasounds]], [[Breast MRI|MRI]] and [[Positron emission mammography|PET]].{{citation needed|date=July 2020}}

[[X-ray]] mammography is widely spread for [[Breast cancer screening|breast screening]], thanks to its high spatial resolution<ref name="Kai-2007">{{cite journal |last1=Yang |first1=Kai |last2=Kwan |first2=Alexander L. C. |last3=Boone |first3=John M. |title=Computer modeling of the spatial resolution properties of a dedicated breast CT system |journal=Medical Physics |date=15 May 2007 |volume=34 |issue=6Part1 |pages=2059–2069 |doi=10.1118/1.2737263|pmid=17654909 |pmc=2838398 |bibcode=2007MedPh..34.2059Y }}</ref> and the short measurement time. However, it is not sensitive to the breast physiology,<ref name="Dobruch-Sobczak-2019">{{cite journal |last1=Dobruch-Sobczak |first1=Katarzyna |last2=Piotrzkowska-Wróblewska |first2=Hanna |last3=Klimoda |first3=Ziemowit |last4=Secomski |first4=Wojciech |last5=Karwat |first5=Piotr |last6=Markiewicz-Grodzicka |first6=Ewa |last7=Kolasińska-Ćwikła |first7=Agnieszka |last8=Roszkowska-Purska |first8=Katarzyna |last9=Litniewski |first9=Jerzy |s2cid=198295706 |title=Monitoring the response to neoadjuvant chemotherapy in patients with breast cancer using ultrasound scattering coefficient: A preliminary report |journal=Journal of Ultrasonography |date=28 June 2019 |volume=19 |issue=77 |pages=89–97 |doi=10.15557/JoU.2019.0013|pmid=31355579 |pmc=6750328 |doi-access=free }}</ref> it is characterized by a limited efficiency in investigating [[dense breasts]]<ref name="Eliot-2010">{{cite journal |last1=Marshall |first1=Eliot |title=Brawling Over Mammography |journal=Science |date=18 February 2010 |volume=327 |issue=5968 |pages=936–938 |doi=10.1126/science.327.5968.936|pmid=20167758 }}</ref> and it is harmful due to the use of [[ionizing radiation]].<ref name="Grosenick-2016">{{cite journal |last1=Grosenick |first1=Dirk |last2=Rinneberg |first2=Herbert |last3=Cubeddu |first3=Rinaldo |last4=Taroni |first4=Paola |s2cid=42000848 |title=Review of optical breast imaging and spectroscopy |journal=Journal of Biomedical Optics |date=11 July 2016 |volume=21 |issue=9 |pages=091311 |doi=10.1117/1.JBO.21.9.091311|pmid=27403837 |bibcode=2016JBO....21i1311G |doi-access=free |hdl=11311/1013563 |hdl-access=free }}</ref> [[Ultrasound]]s are non-invasive and they are used especially on young women,<ref name="Kaplan-2001">{{cite journal |last1=Kaplan |first1=Stuart S. |title=Clinical Utility of Bilateral Whole-Breast US in the Evaluation of Women with Dense Breast Tissue |journal=Radiology |date=December 2001 |volume=221 |issue=3 |pages=641–649 |doi=10.1148/radiol.2213010364|pmid=11719658 }}</ref> who are usually characterized by dense breasts, but the images interpretation depends on the operator's experience. [[MRI]] shows a good correlation with the tumour dimensions  and is claimed to be the best method for the identification and characterization of lesions.<ref name="Hylton-2005">{{cite journal |last1=Hylton |first1=Nola |title=Magnetic Resonance Imaging of the Breast: Opportunities to Improve Breast Cancer Management |journal=Journal of Clinical Oncology |date=10 March 2005 |volume=23 |issue=8 |pages=1678–1684 |doi=10.1200/JCO.2005.12.002|pmid=15755976 }}</ref> Even though there is no verified long-term health risk from the magnetic fields employed during an MRI, it is not used as first investigative tool because of the high costs and the elevated duration of the exam.<ref name="Lord-2007">{{cite journal |last1=Lord |first1=S.J. |last2=Lei |first2=W. |last3=Craft |first3=P. |last4=Cawson |first4=J.N. |last5=Morris |first5=I. |last6=Walleser |first6=S. |last7=Griffiths |first7=A. |last8=Parker |first8=S. |last9=Houssami |first9=N. |title=A systematic review of the effectiveness of magnetic resonance imaging (MRI) as an addition to mammography and ultrasound in screening young women at high risk of breast cancer |journal=European Journal of Cancer |date=September 2007 |volume=43 |issue=13 |pages=1905–1917 |doi=10.1016/j.ejca.2007.06.007|pmid=17681781 }}</ref> Finally, [[Positron emission tomography|PET]] allows the early evaluation of the metabolic changes of the tumour,<ref name="Benard-2005">{{cite journal |last1=Bénard |first1=François |last2=Turcotte |first2=Éric |title=Imaging in breast cancer: Single-photon computed tomography and positron-emission tomography |journal=Breast Cancer Research |date=12 May 2005 |volume=7 |issue=4 |pages=153–62 |doi=10.1186/bcr1201|pmid=15987467 |pmc=1175073 |doi-access=free }}</ref> but it is very expensive and requires the administration of a [[PET radiotracer|radioactive tracer]]. For this reason, its application is not frequently recommended.

On the contrary, optical mammography is cheap, efficient also on dense breasts, and devoid of any side effect, so that it can be used to track the evolution of the patient's condition on a daily basis. It is also able to characterize breast from a physiologic point of view.<ref name="Taroni-2012" /> However, being still under development, there is a lack of standardization in data analysis among the research groups dealing with it, and it suffers from low spatial resolution. For this reason, a "multimodal approach" is suggested, where optical mammography is complementary to another conventional technique, so that also the diagnostic efficacy is improved.<ref name="Grosenick-2016" /><ref name="Taroni-2012">{{cite journal |last1=Taroni |first1=Paola |title=Diffuse optical imaging and spectroscopy of the breast: A brief outline of history and perspectives |journal=Photochem. Photobiol. Sci. |date=2012 |volume=11 |issue=2 |pages=241–250 |doi=10.1039/c1pp05230f|pmid=22094324 }}</ref>

== Physical mechanism ==
=== Photon migration in diffusive media ===
{{See also|Radiative transfer equation and diffusion theory for photon transport in biological tissue}}

Biological tissues are diffusive [[Optical medium|media]], which means that light attenuation during propagation is due not only to [[Absorption (electromagnetic radiation)|absorption]], but also to [[scattering]]. The former is related to the chemical composition of the medium and induces [[photon]] annihilation, whereas the latter depends on the microscopic inhomogeneities of its [[refractive index]] and determines deviations in photon's trajectory.<ref name="Martelli-2009" /> The [[linear attenuation coefficient|absorption coefficient]] <math>\mu_a</math> represents the probability per unit length that an absorption event takes place, while the scattering coefficient <math>\mu_s</math> denotes the probability per unit length that a scattering event occurs.<ref name="Jacques-2013">{{cite journal |last1=Jacques |first1=Steven L |title=Optical properties of biological tissues: a review |journal=Physics in Medicine and Biology |date=7 June 2013 |volume=58 |issue=11 |pages=R37–R61 |doi=10.1088/0031-9155/58/11/R37|pmid=23666068 |bibcode=2013PMB....58R..37J }}</ref> However, many studies refer to the reduced scattering coefficient <math>\mu_s^'=\mu_s (1-g)</math> rather than the simple scattering coefficient, in order to take into account the medium's [[anisotropy]]. The medium's anisotropy is represented by the factor <math>g</math>, which is the average cosine of the angular deflection.<ref name="Martelli-2009" />

Light propagation through highly diffusive media is typically described through the heuristic approach of the [[Radiative transfer|radiative transport theory]], sided by the so-called “[[Radiative transfer equation and diffusion theory for photon transport in biological tissue|diffusion approximation]]”: scattering is assumed to be isotropic and strongly dominant over absorption. This is fairly accurate for example for the breast tissue, in the red and near infrared spectral range (between 600 and 1100&nbsp;nm), known also as "[[Near-infrared window in biological tissue|therapeutic window]]". In the therapeutic window, light can penetrate a few centimetres, so that it can explore the volume at exam. This is the reason why photon migration in biological tissues is known also as "diffuse optics".<ref name="Martelli-2009" />

The relation between reduced scattering coefficient and [[wavelength]] (<math>\lambda</math>) derives from the [[Mie scattering|Mie theory]]:<ref name="Wang-2005">{{cite journal |last1=Wang |first1=Xin |last2=Pogue |first2=Brian W. |last3=Jiang |first3=Shudong |last4=Song |first4=Xiaomei |last5=Paulsen |first5=Keith D. |last6=Kogel |first6=Christine |last7=Poplack |first7=Steven P. |last8=Wells |first8=Wendy A. |title=Approximation of Mie scattering parameters in near-infrared tomography of normal breast tissue in vivo |journal=Journal of Biomedical Optics |date=2005 |volume=10 |issue=5 |pages=051704 |doi=10.1117/1.2098607|pmid=16292956 |bibcode=2005JBO....10e1704W |s2cid=45813277 |doi-access=free }}</ref>

<math>\mu'_s = a  \left( \frac{ \lambda}{\lambda_0}\right)^{-b}</math>

[[File:Breast constituent's absorption spectra.png|thumb|upright=2|Experimental breast constituent's normalized absorption spectra. Hb stands for deoxy-hemoglobin, HbO2 for oxy-hemoglobin.<ref name="Taroni-2017" />]]
where <math>\lambda_0</math> is the reference wavelength and <math>b</math> and <math>a</math> refer to the size of the scattering centres and their density, respectively.

Regarding the absorption coefficient, the relation with <math>\lambda</math> is mediated by the so-called “[[Molar attenuation coefficient|extinction coefficient]]” <math>\epsilon_i(\lambda)</math>,<ref name="Taroni-2015">{{cite journal |last1=Taroni |first1=Paola |last2=Quarto |first2=Giovanna |last3=Pifferi |first3=Antonio |last4=Abbate |first4=Francesca |last5=Balestreri |first5=Nicola |last6=Menna |first6=Simona |last7=Cassano |first7=Enrico |last8=Cubeddu |first8=Rinaldo |last9=Batra |first9=Surinder K. |title=Breast Tissue Composition and Its Dependence on Demographic Risk Factors for Breast Cancer: Non-Invasive Assessment by Time Domain Diffuse Optical Spectroscopy |journal=PLOS ONE |date=1 June 2015 |volume=10 |issue=6 |pages=e0128941 |doi=10.1371/journal.pone.0128941|pmid=26029912 |pmc=4452361 |bibcode=2015PLoSO..1028941T |doi-access=free }}</ref> that in combination with the [[Lambert-Beer law]] gives

<math>\mu_a = \sum_{i} \epsilon_i (\lambda) C_i </math>

where <math>C_i</math> is the concentration of the i{{sup|th}} breast constituent. Measuring <math>\mu_a</math> at different wavelengths, the breast constituents’ concentrations can be extrapolated.

=== Breast constituents' absorption spectra ===
The main breast constituents are [[Hemoglobin|oxy and deoxy-hemoglobin]], [[water]], [[lipid]]s and [[collagen]].<ref name="Taroni-2017">{{cite journal |last1=Taroni |first1=Paola |last2=Paganoni |first2=Anna Maria |last3=Ieva |first3=Francesca |last4=Pifferi |first4=Antonio |last5=Quarto |first5=Giovanna |last6=Abbate |first6=Francesca |last7=Cassano |first7=Enrico |last8=Cubeddu |first8=Rinaldo |s2cid=33523292 |title=Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study |journal=Scientific Reports |date=16 January 2017 |volume=7 |issue=1 |page=40683 |doi=10.1038/srep40683|pmid=28091596 |pmc=5238417 |bibcode=2017NatSR...740683T |doi-access=free }}</ref> In particular, collagen has been recognized as an independent risk factor for developing breast cancer.<ref name="Provenzano-2008">{{cite journal |last1=Provenzano |first1=Paolo P |last2=Inman |first2=David R |last3=Eliceiri |first3=Kevin W |last4=Knittel |first4=Justin G |last5=Yan |first5=Long |last6=Rueden |first6=Curtis T |last7=White |first7=John G |last8=Keely |first8=Patricia J |title=Collagen density promotes mammary tumor initiation and progression |journal=BMC Medicine |date=28 April 2008 |volume=6 |issue=1 |page=11 |doi=10.1186/1741-7015-6-11|pmid=18442412 |pmc=2386807 |doi-access=free }}</ref>

Blood strongly absorbs in the red spectral range, whereas collagen, water and lipids have their absorption peaks at wavelengths longer than 900&nbsp;nm. The distinction between oxy and deoxy-haemoglobin is due to the presence of a second large peak in the case of oxy-haemoglobin. Lipids are characterized by absorption maxima at 930&nbsp;nm and 1040&nbsp;nm, while the wavelength 975&nbsp;nm is sensitive to water. Finally, an absorption peak for collagen takes place at 1030&nbsp;nm.<ref name="Jacques-2013" /><ref name="Taroni-2017" />

== Possible implementations ==
Diffuse optical mammography can be implemented exploiting three different approaches: time domain,<ref name="Taroni-2003">{{cite journal |last1=Taroni |first1=Paola |last2=Pifferi |first2=Antonio |last3=Torricelli |first3=Alessandro |last4=Comelli |first4=Daniela |last5=Cubeddu |first5=Rinaldo |title=In vivo absorption and scattering spectroscopy of biological tissues |journal=Photochemical & Photobiological Sciences |date=2003 |volume=2 |issue=2 |pages=124–129 |doi=10.1039/B209651J|pmid=12664972 |doi-access=free }}</ref> frequency domain<ref name="Durduran-2002">{{cite journal |last1=Durduran |first1=T. |last2=Choe |first2=R. |last3=Culver |first3=J. P. |last4=Zubkov |first4=L. |last5=Holboke |first5=M. J. |last6=Giammarco |first6=J. |last7=Chance |first7=B. |last8=Yodh |first8=A. G. |title=Bulk optical properties of healthy female breast tissue |journal=Physics in Medicine and Biology |date=21 August 2002 |volume=47 |issue=16 |pages=2847–2861 |doi=10.1088/0031-9155/47/16/302|pmid=12222850 |bibcode=2002PMB....47.2847D }}</ref> and continuous wave.<ref name="Matcher-2016">{{cite book |last1=Matcher |first1=Stephen J. |title=Handbook of Optical Biomedical Diagnostics, Second Edition, Volume 1: Light-Tissue Interaction |chapter=Signal Quantification and Localization in Tissue Near-Infrared Spectroscopy |date=25 October 2016 |pages=585–687 |doi=10.1117/3.2219603.ch9 |isbn=9781628419092 }}</ref> Moreover, there exist two main geometries to perform an optical measurement: 

*''Reflectance'': injection and collection occur on the same side of the breast. The woman is usually prone or bent forward and places the breast on a support provided with a hole where sources and detectors are located.<ref name="Jiang-2002">{{cite journal |last1=Jiang |first1=Huabei |last2=Iftimia |first2=Nicusor V. |last3=Xu |first3=Yong |last4=Eggert |first4=Julia A. |last5=Fajardo |first5=Laurie L. |last6=Klove |first6=Karen L. |title=Near-Infrared Optical Imaging of the Breast with Model-Based Reconstruction |journal=Academic Radiology |date=February 2002 |volume=9 |issue=2 |pages=186–194 |doi=10.1016/s1076-6332(03)80169-1|pmid=11918371 }}</ref> Other systems' setups instead require the woman to lie supine and the measurement is carried out with a hand-held probe.<ref name="Xu-2007">{{cite journal |last1=Xu |first1=Ronald X |last2=Young |first2=Donn C |last3=Mao |first3=Jimmy J |last4=Povoski |first4=Stephen P |s2cid=3323560 |title=A prospective pilot clinical trial evaluating the utility of a dynamic near-infrared imaging device for characterizing suspicious breast lesions |journal=Breast Cancer Research |date=18 December 2007 |volume=9 |issue=6 |pages=R88 | pmc=2246191 |doi=10.1186/bcr1837|pmid=18088411|doi-access=free }}</ref>
*''Transmittance'': injection and collection occur on opposite sides of the breast. The breast is usually compressed between plane parallel plates.<ref name="Ferocino-2018">{{cite journal |last1=Ferocino |first1=Edoardo |last2=Martinenghi |first2=Edoardo |last3=Dalla Mora |first3=Alberto |last4=Pifferi |first4=Antonio |last5=Cubeddu |first5=Rinaldo |last6=Taroni |first6=Paola |title=High throughput detection chain for time domain optical mammography |journal=Biomedical Optics Express |date=23 January 2018 |volume=9 |issue=2 |pages=755–770 |doi=10.1364/BOE.9.000755|pmid=29552410 |pmc=5854076 }}</ref><ref name="Enfield-2007">{{cite journal |last1=Enfield |first1=Louise C. |last2=Gibson |first2=Adam P. |last3=Everdell |first3=Nicholas L. |last4=Delpy |first4=David T. |last5=Schweiger |first5=Martin |last6=Arridge |first6=Simon R. |last7=Richardson |first7=Caroline |last8=Keshtgar |first8=Mohammad |last9=Douek |first9=Michael |last10=Hebden |first10=Jeremy C. |title=Three-dimensional time-resolved optical mammography of the uncompressed breast |journal=Applied Optics |date=18 May 2007 |volume=46 |issue=17 |pages=3628–38 |doi=10.1364/AO.46.003628|pmid=17514325 |bibcode=2007ApOpt..46.3628E }}</ref>

Whatever the chosen approach  is, any optical mammograph must comprehend some essential elements: [[laser]] sources, a [[detector]], a [[signal processor]].

The use of multiple laser sources allows to investigate the breast constituents' concentrations of interest, by selecting some specific wavelengths. Detectors are usually [[photomultiplier tube]]s<ref name="Jiang-2002" /> or [[avalanche photodiode]]s.<ref name="Bevilacqua-2000">{{cite journal |last1=Bevilacqua |first1=Frédéric |last2=Berger |first2=Andrew J. |last3=Cerussi |first3=Albert E. |last4=Jakubowski |first4=Dorota |last5=Tromberg |first5=Bruce J. |title=Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods |journal=Applied Optics |date=1 December 2000 |volume=39 |issue=34 |pages=6498–6907 |doi=10.1364/AO.39.006498|pmid=18354663 |bibcode=2000ApOpt..39.6498B |url=http://www.escholarship.org/uc/item/6kq9k3jt }}</ref> Finally, the signal processor could be a device for [[Time-correlated single photon counting]]<ref name="Becker-2004">{{cite book |last1=Becker |first1=Wolfgang |last2=Bergmann |first2=Axel |last3=Biscotti |first3=Giovanni Luca |last4=Rueck |first4=Angelika |s2cid=17283884 |editor3-first=Andreas |editor3-last=Ostendorf |editor2-first=Christopher B |editor2-last=Schaffer |editor1-first=Joseph |editor1-last=Neev |title=Commercial and Biomedical Applications of Ultrafast Lasers IV |chapter=Advanced time-correlated single photon counting techniques for spectroscopy and imaging in biomedical systems |date=2004 |volume=5340 |publisher=International Society for Optics and Photonics |pages=104–112 |doi=10.1117/12.529143 }}</ref> in the case of a time-resolved optical mammograph,<ref name="Ferocino-2018" /> or a filter for frequency modulation in the case of frequency-domain ones.<ref name="Chance-1997" />

Based on the number and position of sources and detectors, an optical mammograph can produce bidimensional or [[Computed tomography laser mammography|three-dimensional]] breast constituents' maps.{{citation needed|date=July 2020}}

=== Time domain ===
{{See also|Time-domain diffuse optics}}

In [[Time-domain diffuse optics|time-domain]] measurements, short light pulses of the order of hundreds of picoseconds are delivered to the breast and its optical properties are retrieved from the features of the re-emitted pulses, which have undergone delay, broadening and attenuation.<ref name="Ferocino-2018" /><ref name="Grosenick-1999">{{cite journal |last1=Grosenick |first1=Dirk |last2=Wabnitz |first2=Heidrun |last3=Rinneberg |first3=Herbert H. |last4=Moesta |first4=K. Thomas |last5=Schlag |first5=Peter M. |title=Development of a time-domain optical mammograph and first in vivo applications |journal=Applied Optics |date=1 May 1999 |volume=38 |issue=13 |pages=2927–43 |doi=10.1364/AO.38.002927|pmid=18319875 |bibcode=1999ApOpt..38.2927G }}</ref> [[Time-correlated single photon counting]] is fundamental to cope with the low-level output signal.<ref name="Becker-2004" />

=== Frequency domain ===
In [[Functional near-infrared spectroscopy|frequency-domain]] measurements, an intensity-modulated signal is injected into the breast and its optical properties are deduced from the dephasement and the demodulation of the output signal with respect to the input one. The measurement is repeated for different values of the frequency modulation.<ref name="Chance-1997">{{cite journal |last1=Chance |first1=B. |last2=Cooper |first2=C. E. |last3=Delpy |first3=D. T. |last4=Reynolds |first4=E. O. R. |last5=Tromberg |first5=Bruce J. |last6=Coquoz |first6=Olivier |last7=Fishkin |first7=Joshua B. |last8=Pham |first8=Tuan |last9=Anderson |first9=Eric R. |last10=Butler |first10=John |last11=Cahn |first11=Mitchell |last12=Gross |first12=Jeffrey D. |last13=Venugopalan |first13=Vasan |last14=Pham |first14=David |title=Non–invasive measurements of breast tissue optical properties using frequency–domain photon migration |journal=Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences |date=29 June 1997 |volume=352 |issue=1354 |pages=661–668 |doi=10.1098/rstb.1997.0047|pmid=9232853 |pmc=1691955 |bibcode=1997RSPTB.352..661T }}</ref><ref name="Moesta-1998">{{cite journal |last1=Moesta |first1=KT |last2=Fantini |first2=S |last3=Jess |first3=H |last4=Totkas |first4=S |last5=Franceschini |first5=MA |last6=Kaschke |first6=M |last7=Schlag |first7=PM |title=Contrast features of breast cancer in frequency-domain laser scanning mammography. |journal=Journal of Biomedical Optics |date=April 1998 |volume=3 |issue=2 |pages=129–36 |doi=10.1117/1.429869 |pmid=23015049|bibcode=1998JBO.....3..129M |doi-access=free }}</ref>

=== Continuous wave ===
In [[Functional near-infrared spectroscopy|continuous wave]] (CW) measurements, the light source is a continuous wave laser, which hinders the separation of the absorption and scattering contributions with a single measurement. A possible solution is to perform space or angle-resolved measurements. In general, the CW approach is combined with the frequency domain one, in order to reinforce the strengths of both.<ref name="Bevilacqua-2000" />

== Potential applications ==
=== Breast cancer risk assessment ===
A denser breast is more likely to develop breast cancer.<ref name="Provenzano-2008" /> A dense breast is characterized by a meaningful amount of fibrous [[Connective tissue|tissue]], relatively to the adipose one. The main constituents of a fibrous tissue are water, collagen and hemoglobin and optical mammography is able to discriminate and quantify tissues' components.<ref name="Taroni-2010" /> Therefore, by measuring breast constituents' concentrations, optical mammography could assess breast cancer risk.<ref name="Taroni-2010" /><ref name="Simick-2004">{{cite journal |last1=Simick |first1=Michelle K. |last2=Jong |first2=Roberta |last3=Wilson |first3=Brian |last4=Lilge |first4=Lothar |title=Non-ionizing near-infrared radiation transillumination spectroscopy for breast tissue density and assessment of breast cancer risk |journal=Journal of Biomedical Optics |date=2004 |volume=9 |issue=4 |pages=794–803 |doi=10.1117/1.1758269|pmid=15250768 |bibcode=2004JBO.....9..794S |doi-access=free }}</ref><ref name="Blackmore-2015">{{cite journal |last1=Blackmore |first1=Kristina M. |last2=Knight |first2=Julia A. |last3=Walter |first3=Jane |last4=Lilge |first4=Lothar |last5=Ho |first5=Yuan-Soon |s2cid=15113061 |title=The Association between Breast Tissue Optical Content and Mammographic Density in Pre- and Post-Menopausal Women |journal=PLOS ONE |date=15 January 2015 |volume=10 |issue=1 |pages=e0115851 |doi=10.1371/journal.pone.0115851|pmid=25590139 |pmc=4295879 |bibcode=2015PLoSO..1015851B |doi-access=free }}</ref>

=== Lesion characterization ===
[[Breast cancer|Tumours]] are generally made of fibrous tissue and could be recognized in the constituents' maps as local spots with higher concentrations of water, collagen and hemoglobin with respect to the surrounding, mostly adipose, healthy tissues. Studies demonstrate that the variation in concentration with respect to the healthy tissue is statistically more marked in the case of malignant tumours than benign ones.<ref name="Leff-2007" /><ref name="Grosenick-2005" /> In addition, the scattering coefficient is generally higher for benign lesions. Such distinctions suggest that optical mammography could characterize breast lesions.<ref name="Leff-2007">{{cite journal |last1=Leff |first1=Daniel Richard |last2=Warren |first2=Oliver J. |last3=Enfield |first3=Louise C. |last4=Gibson |first4=Adam |last5=Athanasiou |first5=Thanos |last6=Patten |first6=Darren K. |last7=Hebden |first7=Jem |last8=Yang |first8=Guang Zhong |last9=Darzi |first9=Ara |s2cid=10705543 |title=Diffuse optical imaging of the healthy and diseased breast: A systematic review |journal=Breast Cancer Research and Treatment |date=28 April 2007 |volume=108 |issue=1 |pages=9–22 |doi=10.1007/s10549-007-9582-z|pmid=17468951 }}</ref><ref name="Grosenick-2005">{{cite journal |last1=Grosenick |first1=Dirk |last2=Moesta |first2=K Thomas |last3=Möller |first3=Michael |last4=Mucke |first4=Jörg |last5=Wabnitz |first5=Heidrun |last6=Gebauer |first6=Bernd |last7=Stroszczynski |first7=Christian |last8=Wassermann |first8=Bernhard |last9=Schlag |first9=Peter M |last10=Rinneberg |first10=Herbert |title=Time-domain scanning optical mammography: I. Recording and assessment of mammograms of 154 patients |journal=Physics in Medicine and Biology |date=7 June 2005 |volume=50 |issue=11 |pages=2429–2449 |doi=10.1088/0031-9155/50/11/001|pmid=15901947 |bibcode=2005PMB....50.2429G }}</ref><ref name="Choe-2009">{{cite journal |last1=Choe |first1=Regine |last2=Konecky |first2=Soren D. |last3=Corlu |first3=Alper |last4=Lee |first4=Kijoon |last5=Durduran |first5=Turgut |last6=Busch |first6=David R. |last7=Pathak |first7=Saurav |last8=Czerniecki |first8=Brian J. |last9=Tchou |first9=Julia |last10=Fraker |first10=Douglas L. |last11=DeMichele |first11=Angela |last12=Chance |first12=Britton |last13=Arridge |first13=Simon R. |last14=Schweiger |first14=Martin |last15=Culver |first15=Joseph P. |last16=Schnall |first16=Mitchell D. |last17=Putt |first17=Mary E. |last18=Rosen |first18=Mark A. |last19=Yodh |first19=Arjun G. |title=Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography |journal=Journal of Biomedical Optics |date=2009 |volume=14 |issue=2 |pages=024020 |doi=10.1117/1.3103325|pmid=19405750 |pmc=2782703 |bibcode=2009JBO....14b4020C }}</ref><ref name="Zhu-2005">{{cite journal |last1=Zhu |first1=Quing |last2=Cronin |first2=Edward B. |last3=Currier |first3=Allen A. |last4=Vine |first4=Hugh S. |last5=Huang |first5=Minming |last6=Chen |first6=NanGuang |last7=Xu |first7=Chen |title=Benign versus Malignant Breast Masses: Optical Differentiation with US-guided Optical Imaging Reconstruction |journal=Radiology |date=October 2005 |volume=237 |issue=1 |pages=57–66 |doi=10.1148/radiol.2371041236|pmid=16183924 |pmc=1533766 }}</ref>

=== Therapy monitoring and prediction of therapy outcome ===
[[Breast cancer management]] depends on the characteristics of the tumour and the patient's condition. One of the possible strategies is the administration of [[neoadjuvant therapy]], whose goal is to shrink the tumour size before surgery.<ref name="Wang">{{cite journal |last1=Wang |first1=Shushu |last2=Zhang |first2=Yi |last3=Yang |first3=Xinhua |last4=Fan |first4=Linjun |last5=Qi |first5=Xiaowei |last6=Chen |first6=Qingqiu |last7=Jiang |first7=Jun |s2cid=6217814 |title=Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors |journal=World Journal of Surgical Oncology |date=2013 |volume=11 |issue=1 |pages=166 |doi=10.1186/1477-7819-11-166 |pmc=3728037 |pmid=23883300 |doi-access=free }}</ref> Studies show that if the therapy is efficient, then the water, collagen and hemoglobin contents of the lesion show a decreasing behaviour over time, which suggests that the initially fibrous tissue acquires features similar to the adipose one.<ref name="jiang-2009" /><ref name="Soliman-2010">{{cite journal |last1=Soliman |first1=H. |last2=Gunasekara |first2=A. |last3=Rycroft |first3=M. |last4=Zubovits |first4=J. |last5=Dent |first5=R. |last6=Spayne |first6=J. |last7=Yaffe |first7=M. J. |last8=Czarnota |first8=G. J. |s2cid=1275542 |title=Functional Imaging Using Diffuse Optical Spectroscopy of Neoadjuvant Chemotherapy Response in Women with Locally Advanced Breast Cancer |journal=Clinical Cancer Research |date=20 April 2010 |volume=16 |issue=9 |pages=2605–2614 |doi=10.1158/1078-0432.CCR-09-1510|pmid=20406836 |doi-access=free }}</ref> Optical measurements in correspondence with therapy sessions could track its evolution, so to assess the patient's response to it. Moreover, it is believed that therapy effectiveness could be predicted even on the first day of treatment on the base of initial breast constituents' concentrations.<ref name="Roblyer">{{cite journal |last1=Roblyer |first1=D. |last2=Ueda |first2=S. |last3=Cerussi |first3=A. |last4=Tanamai |first4=W. |last5=Durkin |first5=A. |last6=Mehta |first6=R. |last7=Hsiang |first7=D. |last8=Butler |first8=J. A. |last9=McLaren |first9=C. |last10=Chen |first10=W.-P. |last11=Tromberg |first11=B. |title=Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment |journal=Proceedings of the National Academy of Sciences |date=18 August 2011 |volume=108 |issue=35 |pages=14626–14631 |doi=10.1073/pnas.1013103108|pmid=21852577 |pmc=3167535 |bibcode=2011PNAS..10814626R |doi-access=free }}</ref><ref name="Cerussi-2007"/>

== See also ==
* [[Breast imaging]]
* [[Diffuse optical imaging]]
* [[Optical tomography]]
* [[Radiative transfer equation and diffusion theory for photon transport in biological tissue]]
* [[Near-infrared window in biological tissue]]
* [[Time-domain diffuse optics]]
* [[Computed tomography laser mammography]]


== References ==
{{reflist}}

{{Medical imaging}}

[[Category:Breast imaging]]
[[Category:Optical imaging]]