Category Archives: FEMALE IMAGING

imaging of different female modalities

MRI DUCTAL CARCINOMA IN SITU (DCIS)

Introduction:

Ductal Carcinoma in Situ (DCIS) is the most common non-invasive type of breast cancer nowadays.

It’s more commonly affect women older than 50 years. Yet prevalence age of DCIS is 32.5 per 100,000 women, this rate jumps to 88 per 100,000 women between the ages of 50 and 64 years.35

its imaging management has wide variation and competition between different imaging modalities.

Ultrasound and mammography are very good in the assessment of DCIS. but nowadays after great advancement of MR technology.

MR overcome the drawback of ultrasound and underestimation of the tumor. So, MRI now is the most sensitive and most accurate way of diagnosis of DCIS.

DCIS isn’t life-threatening when well diagnosed and treated, but if not well managed it can develop invasive breast cancer later on.32

Pathology and clinical condition of DCIS:

Ductal Carcinoma in Situ (DCIS) is a clonal proliferation of malignant epithelial cells originating in terminal duct lobar unit without invasion of the basement membrane2.

DCIS can be multi-focal, (it appears > 1 site within 4 – 5 cm). Or Multi-centric(it appears > 1 quadrant separated by 4-5 cm).

Central necrosis dividing DCIS into comedo-carcinoma which have central necrosis and non-comedo-carcinoma which doesn’t have.

DCIS classify intro three grading:

1-Low-grade it refers to low nuclear grade with the absence of necrosis.

It contains monomorphous, small nuclei with or very few mitosis that causes expansion of the duct (3).

It contains No or few Apoptotic bodies, nuclei are usually diploid. (4).

it’s most commonly present as punctate or rounded calcifications, which is not as much as the extent of the lesion, unlike High-grade type. (3)

DCIS has architectural subtypes: Cribriform, Papillary, micropapillary and solid. The first two types are more common with low-grade type. (4)

2-The intermediate type characterized by a focal area of necrosis (not central necrosis), they tend to be noncomedo-carcinoma.

3- Hight grade type has pleomorphic nuclei 2.5-3 times more than the size of red blood cell (>15 microns). They also comedo-carcinoma as they have central necrosis in duct lumens. (4)

Clinical presentation :

Most DCIS patients are Asymptomatic but when there are symptoms, they come with a palpable mass and nipple discharge.

These are more common in Comedo than Non-Comedo type and it’s more to have micro-invasion and lymph node involvement.(5)

MRI sequences of Localize and characterizations of DCIS:

MRI is the most sensitive and accurate investigation of choice for detecting DCIS (up to 92
% sensitivity for DCIS) (6).

A) DYNAMIC CONTRAST ENHANCED (DCE) MRI SEQUENCES;

The Aim of the MRI detects the tumor and its extent, So the thickness of the slice of the scan ≤ 3 mm, the resolution ≤ 1mm, this leads to decrease volume averaging, making the MR able to make 3D images which much better than 2D images in detecting small tumors . 31

Fat suppression is very effective in detecting DCIS as the MR tumor detection depend on subtraction of pre- & post contrast sequences.

At T1WI pre-contrast, the breast emit a fatty bright signal which may lead under- or over assessment of the lesion31. But removing fat signal, then using subtraction images will lead to more accurate detecting enhancing tumors.

DCIS has MR appearance of mass enhancement or clumped ring enhancement (figure 1and 3 and4), as it raises inside milk ducts, so it follows the ductal tracts and it appears in ductal or regional or segmental distribution

1) T1 WI SEQUENCES:

T1-weighted sequences performed both before & after contrast injection. (associated with fat suppression), this lead to increase spatial and temporal resolution and decrease minimizing section thickness as follows:

MR tumor detection depends on subtraction of pre- & post contrast sequences, At T1WI pre-contrast: breast emit a fatty bright signal which may lead under- or over assessment of the lesion31. But removing fat signal, then using subtraction images  more accurate to detect enhancing tumors.

Most often, these sequences are performed in the axial or sagittal plane as fellow: 30
I) T1WI Axial fast spoiled gradient-echo imaging (TE/TR, 4.2/150) as in figure (2).

II) T1 WI Sagittal fast spoiled gradient echo imaging (TE/TR, 4.2/9) as in figure (2).

III) T1 WI Sagittal fat-saturated imaging (TE/TR,3.2/6.6).

IV) Pre-contrast T1 axial 3D with fat suppression, (mask images for
subtraction).

V) Post-contrast T1 axial dynamic multiphase 3D sequence with fat-suppression (6
acquisitions).

2) T2 WI SEQUENCES:

these increase specificity of MR to detection of DICS, as it appears iso to the-intense at noncontrast T2WI32 .T2WI sequences are the best to visualize breast anatomy and skin and it’s sensitive to fluid 31

I) T2WI Sagittal fast spin-echo fat-suppressed imaging (TE/TR, 88/3000) through both
Breasts.

II) T2WI Axial 2D fast spin echo: (TE/TR,3.3/6.8)

3) KUHL ENHANCEMENT CURVES,

These curves represent contrast uptake into breast lesions rate which is variable according to its nature, very helpful when used in association with morphologic features to get a better diagnosis . as shown in figure (6)

I) First curve called persistent curve: show prolonged signal increase along with time.indicate Benign lesions up to 90%. (11)

II) The second curve is called “Plateau” pattern curve start by increase signal then steady of the curve along with time. Probable malignant lesions obsess this curve(11).

III) The third curve is called: “washout” pattern curve, begin with increasing curve then it falls until end of the curve along with time. This curve indicates high possible malignant lesion. (12)(13)
DCIS has many subtypes of pathology and therefore its presence on MR different widely, But most of DCIS have plateau curves, some have washout curve. (6)

Figure (1) RT side: T1WI pre-contrast Sagittal MR image of Lt breast shows an area of enhancement with no abnormality. Lt side: T1WI Sagittal early post-contrast reveals foci of clumped enhancement (arrowhead) with nearby ductal enhancement (arrow) at the 12 o’clock position. Histopathology reveals DCIS.30

 

Figure (2): 2 Rt Image: axial early post-contrast T1WI fat-suppressed 3D fast spoiled gradient-recalled echo images reveals area of ductal & clumped enhancement (arrows) Lt Image: Sagittal delay post-contrast T1WI of the same lesion. Histopathology reveals DCIS 2

 

Figure (3):
Rt Image: T2WI Sagittal; shows high non mass signal intensity in ductal distribution(11)
Left Image: T1WI Sagittal delayed postcontrast; shows high clumped enhancement in ductal distribution. (11)

 

Figure (4): T1WI Axial fat saturation post-contrast reveals homogenous non-mass enhancement that has segmental distribution., pathology revealed comedo-necrosis High-grade DCIS 11)

 

Figure (5): Transverse T1-WI contrast-enhanced GRE subtracted MR images
of Rt breast, with morphologic characteristics suggestive of (DCIS), look at nonmass enhancement (white arrow )34

Figure (6): shows kinetic enhancement curve analysis show three different type of curves. (6)

 

B) DIFFUSED WEIGHTED IMAGING (DWI):

It now has a promising role in breast tumors differential diagnosis .as ADC level has lower value in malignant than benign tumours10.

But unfortunately, DWI-MR has a limited role indefinite diagnosis of DCIS (figure 7) as the nation mass enhancement that characterizes the DCIS can’t be well assessed with small ROI due to diffuse tumor effect and partial volume effect20.

But it ‘s very helpful when combining DWI with other MR sequences.20

Figure (7): Upper Rt Image: Sagittal 3D T1WI CE fat-suppressed reveals Pre-pectoral enhanced spiculated mass in Rt breast.28


Upper Lt Image: Applying of color enhancement kinetics map reveals tumor with kinetic type II in the center (yellow color) and type I in the periphery (blue color).28


Middle Image: Axial DWI isotropic (b: 700 s/mm2) image reveal high signal intensity within
the mass28


Lower Image: Axial ADC color map image (10.3.5) show restriction of diffusion of the mass with an ADC value of 1.21 × 10−3 mm2/s (ROI number 1)28

C) MR ELASTOGRAPHY

used in the breast tumors to differentiate between Malignant and benign tumors, (10).

Malignant tumors have lower elasticity and the less malignant have more elasticity.

so it’s very helpful in differential diagnosis of DCIS and invasive ductal carcinoma as the invasive ductal carcinoma is very stiff 33.

When used with Dynamic contrast-enhanced MRI, it raises its specificity up to 90 % in detection DCIS (14)

MRI sequences used to plan treatment, assess the completeness of treatment and detect a change in the lesion.

MR is the most sensitive module in determining tumor response to treatment and detecting residual lesions after chemotherapy and before surgery.

MRI can overcome other investigations problems at this point (for example, fibrosis mimic residual at ultrasound).

A) CONVENTIONAL MRI SEQUENCES:

by measuring the changing size of a tumor. but it can’t detect early assessment of treatment response.(20)

B) DYNAMIC CONTRAST ENHANCED MRI:

injection of contrast material with concentration 0.1-0.2 ml/kg. 9This includes taking T1WI post-contrast sequences and compare it with pre-contrast T1WI and T2WI, then we take T2WI post-contrast sequence to reach too high specificity(10)

we use the difference in enhancement kinetic curves parameters to measures the early response of DCIS to chemotherapy with 2 weeks early (10).

There is constantly called Transfer constant, Ktrans.10 we can use it predict the response of DCIS to chemotherapy(15).and vascular disruptive agents or antiangiogenic drugs response to treatment when there is change more than 40%, it’s considered a good response.(16)

C) MR-SPECTROSCOPY:

Its idea base on un-paired protons atoms like Hydrogen (1H), we use its properties of nuclear spin in MR field to absorb and emit radiofrequency(10), as Example 1H MRS enough water suppression is obligatory to detect proton resonances within Cells that increase in cancer, such as choline and lipids.

Choline is invisible and not detected in the normal breast at peak at 3.25 ppm indicates No malignancy (17). Recent studies show very good results, as decrease choline signal after 2 cycles of chemotherapy (figure 8), making MRS more sensitive in detected tumor size changing (18) and even more sensitive than DWI in predicting and detecting the pathological response.(19)

Figure (8): an example of MR-S; A) indicate responders and non-responders after chemotherapy cycle by the level of total choline. the responders begin with high choline level, then markedly decrease. B) indicate an example of lesion monitored after 4 cycles of chemotherapy. (9)

D) DIFFUSED WEIGHTED IMAGING (DWI):

ADC is very effective in predicting the early response of DCIS to treatment than the usual measurement of tumor size changing (20). Increase ADC level means good response to treatment (21)(22).

The main drawback of DWI is that the high signal intensity in cases of DCIS doesn’t get accurate differentiation between it and malignant lesions, so it’s advised to use with other sequences as a figure (7). (20)

E) MRI, T2*/BOLD:

this is Blood oxygen level-dependent (BOLD), the whole idea of this sequence is the use of Deoxyhaemoglobin as a contrast agent to detect the degree of hypoxia of tissue.

This revealed that the tumor tissue is less hypoxic than normal breast tissue. (20it can be used to detected tumor response to treatment although it’s less efficient than other sequences. (24)

MRI Sequences used to grade DCIS:

DCIS is graded into three main categories Low Grade, Intermediate grade, and high-grade DCIS. Sequences :

A) DYNAMIC CONTRAST ENHANCED MRI:

this is the most accurate in detecting different grading of DCIS(20), but its limitation is that contra-indicated with a patient having an allergy to the contrast media or any other contrast related problems. (20)

B) T1WI AND T2WI WITHOUT CONTRAST:

in case of contrast contra-indicated cases. it has low accuracy than DCE-MRI but it’s still good and can be used to avoid the contrast problems. (20)

C) DIFFUSED WEIGHTED IMAGING (DWI):

it’s the sequence of choice in grading DCIS as it doesn’t need contrast so we avoid the contrast problems(20), and it’s easy to process and have short acquisition time. although DCE-MR is more accurate, DWI can’t replace it, but it’ superior to it as it overcomes contrast limitation problems (20). DWI also can also diagnosis and grade DCIS even in the dense breast. (20)

Treatment options and outcomes for the patient:

To get away all risks of DCIS treatment we should ensure as much as the possible complete removal of the tumor. and prevent its recurrence (25). But treatment differs variably according to size, grade, patient age, family history; so, it may include surgery and radiotherapy. L.N removal surgery or hormonal therapy.

A-Surgery:

when we talk about surgery we mean to mention two types of surgery according to DCIS size if small DCIS, so conservative breast surgery or lumpectomy is done. If large DCIS, mastectomy is done. Usually, a simple mastectomy is of choice in most cases then we are going to the adjuvant therapy (chemotherapy or radiotherapy) (25).

B-Radiotherapy:

it’s used in associated / after conservative breast surgery. it has an important role in that. (5)

C- Hormonal therapies:

it helps in a reduced rate of local recurrence rates in DCIS patients. It’s standard now for estrogen & most prog receptor-+ve DCIS. (6)

Outcome: 5- year survival of in-situ patients give 100% five-year survival rate, death rate < 0.7%. (6)

MRI Recurrence Monitoring sequences:

MR is not routinely performed in monitoring recurrence of DCIS as it may overestimate the detected lesion, so it’s considered as good negative (as if MR don’t detect lesion recurrence it’s considered negative for recurrence ) but not good positive sequences.

MRI sequences used in monitoring recurrence are as follows :

A) DCE-MR sequences can accurate detection of any new lesion.The sequences include: Un-enhanced and two contrast-enhanced T1WI fat suppression 3D fast spoiled gradient recall sequence 36 Figure (9)

B) DWI-MR sequences: these play a major role in monitoring recurrence as measurements of ADC is very helpful in differentiation between scar tissue and tumor recurrence. Average ADC value of recurrences was statistically lower of scarring (p < 0.001). (26)

Figure (9):37 MR imaging features comparison between
a, b) a 41-year-old woman with recurrence after definitive surgical treatment for DCIS and
(c, d) the matched 45-year-old control subject

MR images in

(a) Subtracted maximum intensity projection shows increased BPE (background parenchymal enhancement), which measured as mean BPE of 86%. The BPE measurement excludes the known DCIS lesion in the ipsilateral breast (arrow).

(b) SER (signal enhancement ratio )map with color overlay shows a peak SER of 1.57 and an FTV (functional tumor volume )of 8.69 cm3 were calculated from kinetics data. Blue indicates persistent delayed enhancement
(SER,0.9); green, plateau enhancement (SER, 0.9–1.1); and red, washout (SER .1.1).

(c) Subtracted maximum intensity projection for the matched control subject shows minimal BPE (arrow), which measured as mean BPE of 71%.

(d) SER map with color overlay shows a peak SER of 1.17 and an FTV of 1.27 cm3 were calculated from kinetics data. 37

 

Conclusion:

MRI Imaging different sequences are the best investigation of choice for detection and characterization of DCIS and detecting its tumor response to treatment, but they are not ideal for monitoring tumor recurrence.

 

 

References:

1) Gary Liney. MRI in Clinical Practice. Library of Congress Control Number: 2005930807. ISBN-13: 978-1-84628-161-7. Springer-Verlag London Limited 2006.

2) Sughra Raza, Monica Vallejo, Sona A. Chikarmane, Robyn L. Birdwell. Pure Ductal Carcinoma in Situ: A Range of MRI Features. AJR:191, September 2008. JR 2008; 191:689–699.0361–803X/08/1913–689 © American Roentgen Ray Society.

3) Jennifer A. Harvey and David E. March. Making The Diagnosis: A Practical Guide To Breast Imaging .by Saunders, an imprint of Elsevier Inc-2013. ISBN: 978-1-4557-2284-6.

4) Wendie A. Berg, Diagnostic Imaging: Breast, 1st ed. Amity inc2006, printed in Canada; first edition (2006), ISBN-13: 978-1-4160-3337-0.

5) Bassett, Mahoney, Apple, D’Orsi. Ductal Carcinoma in Situ and Paget’s Disease, Breast Imaging by Saunders, an imprint of Elsevier Inc 2011. ISBN: 978-1-4160-5199-2.

6)Lisa A. Newman, Jessica M. Bensenhaver. Ductal Carcinoma In Situ and Microinvasive/
Borderline Breast Cancer. Springer Science+Business Media New York 2015. ISBN 978-1-4939-2035-8.

7) Kilic F, Ogul H, Bayraktutan U, et al. Diagnostic Magnetic Resonance Imaging of the Breast. The Eurasian Journal of Medicine. 2012;44(2):106-114. doi:10.5152/eajm.2012.24.

8) M. Elmaoğlu and A. Çelik, MRI Handbook: MR Physics, Patient Positioning, and Protocols, DOI 10.1007/978-1-4614-1096-6_11,© Springer Science+Business Media, LLC 2012.

9) P. B. Barker, A. Bizzi, N. de Stefano, R. Gullapalli, D. D. M. Lin. Clinical MR Spectroscopy
Techniques and Applications. Published in the United States of America by Cambridge University Press 2010, New York. ISBN-13 978-0-521-86898-3.

10) O’Flynn EA, deSouza NM. Functional magnetic resonance: biomarkers of response in breast cancer. Breast Cancer Research : BCR. 2011;13(1):204. doi:10.1186/bcr2815. Available at:

11) Jeremy Price. Handbook of Breast MRI. Published in the United States of America by Cambridge University Press, New York. 2012 (1st ed). ISBN 978-0-521-13966-3.

12) Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic accuracy, and transfer to clinical practice. Radiology. 2007;244 (2): 356-78.

13) Kuhl CK. Current status of breast MR imaging. Part 2. Clinical applications. Radiology. 2007;244 (3): 672-91.

14) Siegmann KC, Xydeas T, Sinkus R, Kraemer B, Vogel U, Claussen CD Diagnostic value of MR elastography in addition to contrast-enhanced MR imaging of the breast-initial clinical results.
Eur Radiol. 2010 Feb; 20(2):318-25.

15) Ah-See ML, Makris A, Taylor NJ, Harrison M, Richman PI, Burcombe RJ, Stirling JJ, d’Arcy JA, Collins DJ, Pittam MR, Ravichandran D, Padhani AR. Early changes in functional dynamic magnetic resonance imaging predict for pathologic response to neoadjuvant chemotherapy in primary breast cancer. Clin Cancer Res. 2008 Oct 15; 14(20):6580-9.

16) O’Connor JP, Jackson A, Parker GJ, Jayson GC.DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Br J Cancer. 2007 Jan 29; 96(2):189-95.

17) Tozaki M. Proton MR spectroscopy of the breast.Breast Cancer. 2008; 15(3):218-23.

18) Tozaki M, Sakamoto M, Oyama Y, Maruyama K, Fukuma E .J Magn Reson Imaging.Predicting pathological response to neoadjuvant chemotherapy in breast cancer with quantitative 1H MR spectroscopy using the external standard method.. 2010 Apr; 31(4):895-902.

19) Tozaki M, Oyama Y, Fukuma E Jpn J Radiol.A preliminary study of early response to neoadjuvant chemotherapy after the first cycle in breast cancer: comparison of 1H magnetic resonance spectroscopy with diffusion magnetic resonance imaging.. 2010 Feb; 28(2):101-9.

20) Bachir Taouli. Extra-Cranial Applications of Diffusion-Weighted MRI. Published in the United States of America by Cambridge University Press, New York. © Cambridge University Press 2011. ISBN-13 978-0-521-51869-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109577/#B8

21) Sharma U, Danishad KK, Seenu V, Jagannathan NR.A longitudinal study of the assessment by MRI and diffusion-weighted imaging of tumor response in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. NMR Biomed 2009;22 (1):104–13.

22) Nilsen L, Fangberget A, Geier O, Olsen DR, Seierstad T.Diffusion-weighted magnetic resonance imaging for pretreatment prediction and monitoring of treatment response of patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy.
Acta Oncol. 2010 Apr; 49(3):354-60.

23) Alonzi R, Padhani AR, Maxwell RJ, Taylor NJ, Stirling JJ, Wilson JI, d’Arcy JA, Collins DJ, Saunders MI, Hoskin PJ. Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans.Br J Cancer. 2009 Feb 24; 100(4):644-8.

24) Li SP, Taylor NJ, Makris A, Ah-See ML, Beresford MJ, Stirling JJ, d’Arcy JA, Collins DJ, Padhani AR. Primary human breast adenocarcinoma: imaging and histologic correlates of intrinsic susceptibility-weighted MR imaging before and during chemotherapy.Radiology. 2010 Dec; 257(3):643-52.

25) Mohammed Badruddoja. Ductal Carcinoma In Situ of the Breast: A Surgical Perspective. Hindawi Publishing Corporation.International Journal of Surgical Oncology.Volume 2012, Article ID 761364, 12 pages.doi:10.1155/2012/761364.

26) Rinaldi P1, Giuliani M, Belli P, Costantini M, Romani M, Distefano D, Bufi E, Mulè A, Magno S, Masetti R, Bonomo L. DWI in breast MRI: the role of ADC value to determine diagnosis between recurrent tumor and surgical scar in operated patients.Eur J Radiol. 2010 Aug;75(2):e114-23. doi: 10.1016/j.ejrad.2010.01.018. Epub 2010 Feb 20. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20172677.

27) Breast cancer statistics, Breast cancer in Australia, The Australian government, Cancer Australia. available at:https://breast-cancer.canceraustralia.gov.au/statistics.

28) Antonio Luna, Ramón Ribes, Jorge A. Soto. Diffusion MRI Outside the Brain, A Case-Based Review, and Clinical Applications. Springer-Verlag Berlin Heidelberg 2012. Library of Congress Control Number: 2011933937.e-ISBN 978-3-642-21052-5.DOI 10.1007/978-3-642-21052-5.

29) Raikhlin A, Curpen B, Warner E, Bethel C, Wright B, Jong R. Breast MRI as an Adjunct to Mammography for Breast Cancer Screening in High-Risk Patients: Retrospective Review. American Journal of Roentgenology. 2015;204(4):889-897.

30) Mossa-Basha M, Fundaro G, Shah B, Ali S, Pantelic M. Ductal Carcinoma in Situ of the Breast: MR Imaging Findings with Histopathologic Correlation. RadioGraphics. 2010;30(6):1673-1687.

31) Shahid H, Wiedenhoefer JF, Dornbluth C, Otto P, Kist, KA. An overview of breast MRI. Appl Radiol. 2016;45(10):7-13. October 15, 2016.

32) Nadrljanski, Mirjan M., Biljana B. Marković, and Zorica Č. Milošević. “Breast Ductal Carcinoma in Situ: Morphologic and Kinetic MRI Findings.” Iranian Journal of Radiology 10.2 (2013): 99–102. PMC.

33) Siegmann, K.C., Xydeas, T., Sinkus, R. et al. Eur Radiol (2010) 20: 318. Springer-Verlag.
Print ISSN0938-7994.Online ISSN1432-1084.

34) Pediconi F, Catalano C, Roselli A, Padula S, Altomari F, Moriconi E et al. Contrast-enhanced MR Mammography for Evaluation of the Contralateral Breast in Patients with Diagnosed Unilateral Breast Cancer or High-Risk Lesions1. Radiology. 2007;243(3):670-680.
35) Allegra CJ, Aberle DR, Ganschow P, et al. Diagnosis and management of ductal carcinoma in situ (DCIS). NIH Consens State Sci Statements 2009;26(2):1–27.

36) Luo J, Johnston B, Kitsch A, Hippe D, Korde L, Javid S et al. Ductal Carcinoma in Situ: Quantitative Preoperative Breast MR Imaging Features Associated with Recurrence after Treatment. Radiology. 2017;:170587.

37) Luo J, Johnston B, Kitsch A, Hippe D, Korde L, Javid S et al. Ductal Carcinoma in Situ: Quantitative Preoperative Breast MR Imaging Features Associated with Recurrence after Treatment. Radiology. 2017;:170587.

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