Titanium Contrast-Enhanced Mammography (TiCEM): Mammography Becomes a Functional Technique

Titanium Contrast-Enhanced Mammography (TiCEM): Mammography Becomes a Functional Technique
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Arlette Elizalde, MD and Luis J. Pina Insausti, MD, PhD
Clínica Universidad de Navarra, Pamplona, Spain


Digital Mammography has evolved into more accurate techniques, such as Digital Breast Tomosynthesis and Contrast Enhanced Dual Energy Mammography (CEDEM). CEDEM combines the high spatial resolution of Digital Mammography and the added value of neoangiogenesis. To obtain this functional information, the administration of intravenous iodinated contrast medium is required. A dual energy acquisition is performed: First, a low-energy image (similar to conventional DM) and immediately, during the same compression, a high-energy image is acquired (to detect the contrast uptake). MAMMOMAT Revelation has been developed to perform CEDEM. This system uses a titanium filter instead of a copper filter to reduce the tube load during the high-energy acquisition. For this reason, the contrast enhanced mammography technique is known as TiCEM (Titanium Contrast Enhanced Mammography). In our experience, TiCEM is more accurate than DM and offers morpho-functional information of breast lesions [1].


Mammography-based breast screening is the only breast imaging technique that has been proven to reduce breast cancer mortality [2]. DM offers the highest spatial resolution of all the imaging modalities in a radiology department, being capable of detecting very subtle microcalcifications that can be the first sign of breast cancer. DM is usually the initial examination used in breast imaging and for breast cancer screening because it is a widely available and inexpensive technique. However, DM has a variable sensitivity that ranges from 50% to 85% and is especially low in dense breasts. It is well-known that the sensitivity of DM drops in dense breasts because of the overlapping tissue [3]. This low sensitivity has resulted in the introduction of complementary techniques such as ultrasound and digital breast tomosynthesis (DBT). DBT can significantly increase the sensitivity of DM from 60.4% to 81.1% [4].

Magnetic Resonance Imaging (MRI) of the breast is considered to be the most sensitive technique to detect breast cancer, especially invasive tumors. This high sensitivity is due to the use of intravenous contrast agents (gadolinium-based contrast media). Most breast cancers enhance at 1–2 minutes after the administration of i.v. contrast because of neoangiogenesis, i.e., new vessels with increased permeability. This is the reason why MRI is a morpho-functional technique. However, MRI of the breast is still an expensive technique, with little availability in many centres. Furthermore, it can have high false positive rates because many benign conditions can take up i.v. contrast. Finally, MRI is not always feasible in claustrophobic patients and in a small number of patients with certain metallic devices such as some metal implants, aneurysm clips, or pacemakers.

Contrast-enhanced dual energy Mammography

DM is a purely morphological technique, based on the attenuation of X-ray photons in the tumoral tissue. However, DM can become a morpho-functional technique by using intravenous iodine-based contrast agents. The physiological mechanism for the detection of breast cancer is similar to MRI: the malignant lesions are detected due to neoangiogenesis. However, the contrast uptake of tumors cannot be shown on conventional DM because this technique uses low energy (23–28 kV). A specific energy level is required to detect the contrast agent, which is higher than conventional DM, ranging from 45 to 49 kV. That is why contrast-enhanced mammography uses dual energy: First, a low-energy image is acquired, similar to conventional DM, and immediately after, a high-energy image is also acquired to detect the contrast uptake. Both acquisitions are performed during the same compression. The high-energy image itself does not have diagnostic capabilities due to the high kV, which produces low tissue contrast and has a grey-appearance. For this reason, the system is optimized to create a recombined image by subtracting the low-energy image from the high-energy image.

 1    The MAMMOMAT Revelation performs Digital Mammography (DM), Digital Breast Tomosynthesis (DBT) and Contrast-Enhanced Dual Energy Mammography (CEDEM).

This morpho-functional technique, known as Contrast-Enhanced Dual Energy Mammography (CEDEM), combines the high spatial resolution of DM with the information on neoangiogenesis. Both images, the lowenergy (LE) and the recombined (R) ones, can be easily compared. This is a great advantage, because for one and the same lesion, the morphological and functional information is available at the same time [5].

The MAMMOMAT Revelation (Siemens Healthcare, Forchheim, Germany) uses a titanium filter instead of a copper filter for the high energy acquisition (Fig. 1). The commercial name for the CEDEM technique is TiCEM (Titanium Contrast-Enhanced Mammography). Its major advantage over other CEDEM techniques is better transmission with the same beam hardening, resulting in a reduced X-ray tube load. This allows for seamless examinations as the tube does not heat up as much while maintaining image quality [6].


Indications, contraindications, and risks

TiCEM is not intended to be used for the screening of a low risk population. The reasons are very simple: TiCEM uses i.v. contrast and a vein puncture is needed. Furthermore, the costs of the technique, although clearly lower than MRI, are higher than for DM.

The main indications of TiCEM are:

  • Problem-solving technique: In a diagnostic setting, TiCEM can be used to evaluate palpable masses, asymmetries, mammographically detected masses, architectural distortions or any other doubtful findings on DM, DBT, or US.
  • Assessment of recently diagnosed breast cancers: TiCEM can help in the detection of multifocal, multicentric, or bilateral cancers.
  • Evaluation of response after neoadjuvant chemotherapy.
  • Screening of selected groups: Intermediate risk women are those who have a higher risk of developing breast cancer in the future than the normal population but still have a risk of less than 25% during their lifetime (high risk women). This intermediate risk group comprises patients with a positive family history of breast cancer, some risk histological lesions (the known b3 histopathological lesions such as lobular carcinoma in situ, atypical ductal hyperplasia …), patients with personal history of breast cancer, and those with extremely dense breasts.

 2   81-year-old lady who came to our institution because of a palpable lump in the left breast.The low-energy acquisition shows an irregular spiculated mass.The recombined image shows the enhancing mass and a subtraction of the normal fibroglandular tissue. Pathology: Invasive ductal carcinoma..

 3   A 52-year-old woman attended at our institution with a palpable lump in the right breast. The low-energy image was considered normal. However the recombined image showed a suspicious enhancement, correlated with the palpable mass. Pathology: Invasive duct alcarcinoma.


TiCEM is contraindicated for patients with a known allergy to iodinated contrast agents, pregnant patients, and those with renal insufficiency. Although it is not formally contraindicated, TiCEM is not intended for patients with breast implants or patients who are breast feeding.


The risks of TiCEM derive from the use of iodinated contrast agents. With the latest non-ionic iodinated contrast media, the incidence of hypersensitivity reactions is 0.7–3% [7]. Severe hypersensitivity reactions occur in only 0.02–0.04% of cases [8].

Description of the procedure

TiCEM is routinely performed in the mammography examination room. After a brief anamnesis to rule out allergy to iodinated contrast media, renal insufficiency, or pregnancy, informed consent is obtained. Then, an i.v. catheter is placed in a peripheral vein. An automatic injector is used for the administration of 1.5 mL per kg of iodinated contrast media at a rate of 3 mL per second. A delay is necessary for the perfusion of the contrast after the i.v. bolus (usually two minutes). Then the breast is compressed to obtain the images, usually starting with the pathological side. Several options can be offered: A unilateral study of the problematic breast (craniocaudal and MLO views) or a bilateral study using both views. During the same compression, the system acquires both the low-energy and high-energy images, which are quickly reconstructed and sent to a workstation for interpretation.

Our experience

We started implementing TiCEM examinations in October 2017. This technique was used as a problem solving technique and as an imaging modality to characterize breast lesions previously detected on DM, DBT, or US. Recently, we retrospectively assessed the TiCEM examinations that were performed at our institution. From October 2017 to June 2018, 80 patients with 120 histologically confirmed lesions were recruited. Three readers with different experience level in breast imaging (expertise, intermediate level, resident), blinded to the final diagnoses, evaluated both the low-energy (LE) and the recombined (R) images. The readers classified the lesions according to the BI-RADS categories.

Of the 120 lesions, 41 were benign and 79 malignant. The results were interpreted by means of ROC curves. The Area Under the Curve (AUC) of the combination LE+R was significantly larger than the AUC of LE alone for all the readers (p<0.001), irrespective of the experience of the reader (reader 1: 0.72 vs 0.86; p< 0.001; reader 2: 0.63 vs 0.80; p<0.001; reader 3: 0.70 vs 0.79; p<0.001). These data were similar for dense and non-dense breasts.


TiCEM is a new imaging modality that adds functional information to conventional mammography. This technique shares many of the indications of MRI, with the advantages of lower cost and better availability. In our experience, TiCEM shows better diagnostic accuracy than digital mammography, irrespective of the experience level of the radiologist.



  1. González-Huebra I, Malmierca P, Elizalde A, Etxano J, Vejborg I, Uhlenbrock D, et al. The accuracy of titanium contrast-enhanced mammography: a retrospective multicentric study. Acta Radiol. 2020 [ahead of print].
  2. Tabár L, Vitak B, Chen TH, Ming-Fang A, Cohen, Tot T, et al. Swedish two-county trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 2011;260: 658–663.
  3. Pisano ED, Hendrick RE, Yaffe MJ, Baum JK, Acharyya S, Cormack JB, et al. Diagnostic accuracy of digital versus film mammography: exploratory analysis of selected population subgroups in DMIST. Radiology 2012;246:376–383.
  4. Zackrisson S, Lång K, Rosso A, Johnson K, Dustler M, Förnvik D, et al. One-view breast tomosynthesis versus two-view mammography in the Malmö Breast Tomosynthesis Screening Trial (MBTST): a prospective, population-based, diagnostic accuracy study. Lancet Oncol. 2018 Nov;19(11):1493-1503.
  5. Patel BK, Lobbes MBI, Lewin J. Contrast Enhanced Spectral Mammography: A Review. Semin Ultrasound CT MR 2018;39:70-79.
  6. Knogler T, Homolka P, Hornig M, Leithner R, Langs G, Waitzbauer M, et al. Contrast-enhanced dual energy mammography with a novel anode/filter combination and artifact reduction: a feasibility study. Eur Radiol 2016;26:1575–1581.
  7. Li X, Liu H, Zhao L, Liu J, Cai L, Liu L, et al. Clinical observation of adverse drug reactions to non-ionic iodinated contrast media in population with underlying diseases and risk factors. Br J Radiol 2017;90:20160729.
  8. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology 1990;175:621-8.

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Published on : Thu, 2 Jun 2022

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