Breast MRI contrast enhancement kinetics
When MRI is used for breast cancer screening purposes, the MRI technicians will inject a contrast-enhancing agent into the blood stream, and then observe various kinds of changes or 'enhancements' that may show in the suspected breast cancer lesion. Generally speaking, if there is neoplastic cell growth (possibly breast cancer) these new cells will have developed a 'thirst' for blood supply, and this will appear quite different and distinct from blood use in normal tissue. The term "kinetics" refers to the changes in the contrast (brightness and darkness) in various parts of the lesion as they change over time.
Kinetic phases of Dynamic Contrast Enhancement: Initial peak phase, delayed phase
Essentially there are two phases in the dynamic contrast enhancement MRI observation. First there is the 'intial peak' phase which happens early in the process (under two minutes generally). The radiologist will be watching to see how high or 'intense' the signal (the 'brightness') reaches within the suspicious breast lesion. Once this initial 'peak' is reached, the second phase begins. This is the 'delayed' phase. There are three basic patterns or contours (sometimes called the 'curvature') in the delayed phase. When the signal of the contrast enhanced breast lesion continues to increase in a gradual and linear way (marked "I" in the image above) this might be termed continuing increasing enhancement (which tends to be associatied with benign fibroglandular breast tissue). If the signal intensity stays the same, this is commonly referred to as a 'plateau', (marked with 'II' above). If the signal fades gradually, this is commonly referred to a 'washout' (marked with 'III' above).
Breast cancer MRI studies have demontrated that lesions which appear as 'suspicious' on either mammogram or pre-contrast MRI (usually a mass with spiculated or somewhat random margins is considered the most suspicious for breast cancer) tend to be associated with the delayed kinetics 'washout' profile. It should be noted, however, that evidence for a consistent relationship between kinetic contrast enhancement profile and malignant breast cancer identification is not really in evidence at the present time. The washout pattern has been found in between 45% and 50% of malignant breast cancer lesions in recent studies, which leaves around 1/2 of all malignant breast cancer lesions that cannot be confirmed in this way. The best generalization that can be made at present is that the 'worst looking' kinetic curve (profile) is a rapid contrast enhanced signal intensity increase to about the middle or 'moderate' level, followed by a gradual washout (gradual decrease or fade in the signal) in the delayed phase. This pattern is most likely to be associated with malignant breast cancer.
Fast spin echo T2 weighted breast MRI
In addition to the dynamic MRI sequences, a 'fast spin-echo' T2 weighted sequence also frequently performed in contrast enhanced breast MRIs in order to assess cystic changes or edema which may be present. Most benign breast lesions will show brightly on T2 weighted images.
bilateral vs unilateral MRI dynamic contrast enhancement scans
Even though emphasis is usually placed on a unilateral MRI scan (which places emphasis on analysis of the lesion without sacrificing temporal resolution), bilateral breast MRI examinations do allow for comparision with the contralateral breast tissue. This would include evaluation of the enhancemtn pattern in terms of inflow pohenomenon, any hormonal effects on breast parenchyma, and generally allow control over any inhomogeneities of the MRI exam. Bilateral MRI contrast enhancement analysis is particularly helpful in diagnosing diffuse breast carcinoma, which enhances diffusely and with no particularly dominant mass. So, while bilateral scanning does indeed help detect any incidental contralateral breast cancers that may be present, the drawback is that spatial resolution is sacrificed because the fields of view are increased.
Sensitivty and predictive value of Breast MRI cancer detection
The threshold in which an invasive breast carinoma may be detected with dynamic contrast enhanced MRI is generally thought to be about 3mm, as tumor angiogenesis tends to begin only when the tumor reaches that size.
High power magnets are required for breast cancer screening MRIs
The main advantage of using MRI over mammography is that the contrast resolution is high even in dense breast tissue. High quality equipment is essential however. 1.5 Tesla magnets have a sensitivity of over 95% in detecting breast cancer, while a 1 Telsa machine only has a sensitivity of around 88%. 1.5 Tesla magnets are considered to be the minimal strength required for MRI breast imaging.
Reasons for 'false negative' findings in breast DCE MRIs
Sometimes user errors may account for 'false negative' results on breast MRI scans, but there can also be technical glitches resulting from field inhomogeneity, and motion artifacts as a result of non suppressed images or poor image quality. Sometimes malignant breast cancer lesions lie outside of the field of view (for example very near to the chest wall), and occassionaly the contrast is poor due to the extravasation of contrast material during injection.
False negatives can also result from poor breast lesion histology
A 'false negative' contrast enhanced breast MRI can also be due to histological aspects of the surround breast tissue. With some pre-menopausal women, benign breast tissue might enhance intensely. If there are proliferating breast changes or inflammatory process within the breast, this might also mask a tumor. Very slowly enhancing or non-enhancing carcinoma might be missed, and very small breast cancers may go undetected. Missed cases of breast carcinoma might also be explained by by the poor angiogenesis in some lesions or their more diffuse pattern of growth.
|False negative MRI. Invasive breast carcinoma|
|Histology/Carcinoma type||False negative percentage of cases|
|Invasive Ductal Carcinoma||0|
|Lobular Carcinoma||10.8 %|
|Invasive mixed ductal/lobular breast cancer||0|
|Tubular breast carcinoma||7.7 %|
|Medullary Breast Carcinoma||0|
|Mucinous breast carcinoma||0|
|Others (metastasis and sarcoma)||2.6 %|
We note from the statistics above that invasive lobular carcinoma tends to missed in a contrast enhanced breast MRI the most frequently. Tubular breast carcinoma also tends to have a relatively high level of false negative MRI analysis, while invasive breast cancer is mistaken for sarcoma or metastasis of cancer from another area of the body about 2.6% of the time.
Rate of false negative contrast enhanced MRI and ductal carcinoma in situ.
The rate of missed (false negitive) DCE (dynamic contrast enhanced) MRI assisted diagnosis of DCIS tends to be higher than than for invasive breast carcinomas. With a magnet strength of 1.5 Tesla (1.5 tends to be the minimal power required for valid contrast enhanced breast MRI readings) the rate of false negative (missed) DCIS is about 28% or less. With a magnet strength of only 1.0 Tesla, the false negative rate can be very (unacceptably) high, at up to 65%. Among the possible reasons for missing the presense of DCIS in breast contrast enhanced MRI is that there is perhaps no angiogenesis at that stage. Also, the appearance of DCIS can be non-specific. If the DCIS is of the non-comedo variety, (which is DCIS of a low to intermediate grade) it can also fail to present a compelling signal on the DCE MRI scan. Ductal carcinoma in situ successfully detected using contrast enhancing MRI tend to be larger in size, and may already show 'micro-invasion' beyond the duct wall. Ductal carcinoma in situ tends to demonstrate suspicious microcalcifications on a breast cancer screening mammogram, and even if a contrast enhanced MRI is negative, a biopsy is generally taken anyway.
Invasive breast cancers will tend to show greater neovascularity and arteriovenous anastomoses, which will tend to present with a more rapid and intense initial phase signal. The washout phase of invasive breast carcinoma will also tend to be a little bit faster than with noninvasive breast carcinoma lesions. The washout phase of non-invasive breast cancer (DCIS) tends to be significantly less pronounced.
False positive dynamic contrast enhanced MRI breast lesions
The major source of 'false positive' contrast enhanced MRI findings are non-mass breast lesions. ( Speaking here of the 'morphology' of lesions using contrast enhanced breast MRI. Lesions tend to be either 'focal', non-mass-like, or a mass). It is also of some interest that the diameter of a suspected non-mass-like breast tumor has no difference on the correct diagnosis of malignant breast cancer.
Breast Cancer MRI interpretation is not standardized
At the present time there is no 'global standard' in the aquisition and interpretation of breast MRI and contrast enhanced breast MRI. Since there is no universally applicable standard of 'quality control' it is difficult to make definitive statements as to their interpreation with regards to breast cancer. However, as dynamic contrast enhanced MRI becomes more and more widespread, and providing the kinetic intensity curves are measured in a disciplined way and with well-documented follow up, kinetic phase assessment will likely emerge as a standard breast cancer diagnostic tool in the years to come. The sensitivity of contrast enhanced breast MRI is very high, but the specificity remains very low.
There are significant differences between benign and malignant breast cancer lesions in the rate of uptake, the initial slope, the curvature following peak enhancement ( persistent increase, stays the same, or fades/washes out) and the signal enhancement ratio. Likely what will have to happen to improve the usefulness of the technique is to consistently pair or associate the morphological and kinetic profile of the breast lesion in question with other parameters outside of the MRI domain, such as vascularity for example.
A few breast cancer researchers are presently exploring the notion of 'textural kinetics', which tries to identify and interpret 'spatio-temporal' changes in the texture of the breast lesion. The 'textural kinetics' refer to the internal texture inside of a lump. The radiologist will consider whether the breast lesion is enhancing homogenously or not. They will also consider whether or not the 'rim' of the lesion is enhanceing in a smooth appearance, or whether it is irregular or blotchy. By looking at the texture inside the breast nodule, a radiologist can make informed hypotheses as to the makeup of the internal non-enhancing areas in terms of the presence of fluids or internal necrosis. Considering the textural kinetics, in addition to the signal intensity profile, can yield an even more accurate assessment of the malignant or benign nature of a suspected breast cancer lesion.
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Copyright Steven B. Halls, MD Last edited 24-November-2010