Seite - 109 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Alcantaraet al. Molecular imagingofbreast cancer FIGURE2 |Breastcancerultrasound images. pregnant andbreastfeedingwomen.Moreover, it has high sensi- tivity to show tumormargins and the internal characteristics of tissue, and it is used as complementary technique tomammog- raphy for the study of dense breasts and to assess lymph node status. It isalsofrequentlyusedforbreast intervention, forguided biopsyandfor theplacementofharpoons. Inrecentyears,differ- ent ultrasound techniques for the breast pathology studies have beendeveloped, including: Ultrasoundcontrast Ultrasound contrast involves the intravenous injection of per- fluorocarbon microbubbles to observe the behavior of breast lesions by ultrasound. The perfusion area and the signal inten- sity curves in relation to time are obtained using this method. Ultrasoundcontrast isusedfordiagnosis,detectionofrecurrence andmonitoringof treatment response, and is particularlyuseful as a guide forpunctureof suspicious lymphnodes, asmetastatic lymphnode areas do not capture contrast and can be therefore differentiated fromhealthyareas. On the other hand, 3D ultrasound is particularly useful for the study of breast lesion with contrast, because it allows the assessmentofnodeswith contrast in threedimensions (Jia et al., 2014). Elastography This technique is based on the same principle as breast tender- ness and candetermine thehardness of the lesionbymeasuring the elastic properties of tissues by ultrasound, as the lower the hardness of a lesion, the higher the probability of being benign, andvice versa. Elastographyhasbeen shown tobeveryuseful in the assessment of benign lesions (BIRADS 3) (Itoh et al., 2006; Scaperrottaetal., 2008). MAGNETICRESONANCEIMAGING(MRI) MRI is an important diagnostic tool frequently used to study breastdisease.Itcurrentlyhasspecificindications, includingeval- uationof response to treatment, screening in high-risk patients, study of occult breast cancer, study of tumor recurrence and assessment of breast prostheses.MRI can be also recommended for the staging of breast cancer, the study of microcalcifica- tions, breast discharge, premalignant lesions, residual tumor in operated patients or in case of inconclusive findings by mam- mography and ultrasound (Mann et al., 2008; Sardanelli et al., 2010). TheMRI techniques applied to the studyof breast cancer are based on both the assessment of themorphological features of the lesions and the characteristics of contrast enhancement of these lesions.Malignant tumorshaveadisorganizedangiogenesis showingspecificmorphologicalandfunctionalcharacteristics. TheMRI study includes pre-contrast T2 sequences andpost- contrast 3D T1-weighted gradient Eco. Several parameters are analyzed inthecontrast studies, suchas theslopeof theenhance- ment curve during both the uptake and wash out phases, the timetopeakenhancementor themaximal relativeenhancement. These analyses can differentiate benign frommalignant lesions. Image post-processing plays an important role in dynamic con- trast MRI because it provides the radiologist with additional parametric information that can be crucial for a more accu- rate diagnosis. Thus, typical post-processing processes include subtraction of images, projections ofmaximum signal intensity (MIP), multiplanar reconstructions (MPR) and time curves of suspicious lesionsuptake(Kuhl,2007;Partridge,2008). Currently, there are two classification systems for the diag- nostic criteria in breast MRI: the Fischer and the ACR classi- fications. Both present common diagnostic criteria, integrating morphologicalanddynamicuptakeinformation.TheACRclassi- ficationpresentscommoncriteriawith theBIRADSclassification ofmammographyandultrasound(Agrawaletal.,2009;MorrisEa etal., 2013).During the last fewyears,otherMRtechniqueshave been proposed for the study of breast cancer, namely diffusion MRIandspectroscopy. DiffusionMRI DiffusionMRI techniques are based on the application of field gradients to enhance the signal lost due to theBrownianmotion ofwatermolecules.Thediffusionweighting isdeterminedby the strength and duration of the diffusion gradients, and the time between the gradient pulses, which is all quantified by the b- factor. The exponential fit of signal intensity vs. the b values provides the apparent diffusion coefficient (ADC), whose val- ues reflect the restriction of water motion in any given tissue and, in the case of tumor growth, it has been related to cellular- ity.Malignant tumorsusuallyhavehigh cellularity and therefore present lowADCvaluesascomparedtobenignlesions.Diffusion MRIisaquicktechniquethatdoesnotrequire theuseofcontrast agentsanditsimplementationhasbeenrecommendedaspartofa routineprotocolforbreastMRI.Themaindisadvantagesofdiffu- sionMRIare the lowspatial resolutionandthe lackof specificity todifferentiatebetweenbenignandmalignanttumors(Guoetal., 2002;Petersetal., 2008). MRspectroscopy Breast spectroscopy provides information about the metabolic profile of tumor tissue, being themost importantmetabolite in breast spectroscopy tCho (total choline),whichhas been related to tumorproliferationactivity.Theuseof spectroscopyhasbeen shown to increase the specificity ofMRfor thedifferentiationof benignandmalignantlesions.Severalstudiesindicatetheassocia- tionbetweenthecholinepeakwiththeresponsetothetreatment. In this sense, Tozaki et al. (2010) found that the reduction of choline peak is more sensitive to determining the response to www.frontiersin.org December2014 |Volume2 |Article112 |109