The phenomenon of nuclear magnetic resonance (NMR) was discovered and studied in the 1950s of the twentieth century. Two groups of British physicists under the leadership of Bloch and Pursell determined physical and chemical factors, such as proton density and the so-called relaxation parameters, times of longitudinal (T1) and transverse (T2) substance relaxation, on which the value of the detected MR signal depended. Hahn (1950) developed an in vitro method for measuring the substance relaxation parameters using a sequence of radio pulses, called a pulse sequence (PS) “spin echo” (SE) (Hahn 1950; Bloch et al. 1946; Pursell et al. 1946).

In 1973 Lauterbour proposed to separate the MR signal from a layer inside an object with an additional magnetic field G _z , changing linearly with distance in the direction of the main magnetic field of the magnet (gradient magnetic field). In the same year, Mansfield established a link between the frequency (phase) change of MR signals and the coordinates of voxels in the layer. He used two additional mutually perpendicular gradient magnetic fields G _х and G _у to set the coordinates of each element in the tomographic section and applied the Fourier analysis to extract MR signals from the registered data from each voxel in a given layer. This approach allowed to reduce the time obtaining tomographic cross sections down to a few minutes (Mansfield 1977). Lauterbour and Mansfield were awarded the Nobel Prize in Physiology or Medicine Prize in 2003 for the creation of MR imaging methods that were implemented in modern MRI scanners.

A detailed description of NMR physics and imaging principles intended for diagnosticians can be found in many monographs (Edelman et al. 1996; Konovalov et al. 1997a, b, c; Rink 2003).

A variety of tissue contrast ranges in MR images provide a wide set of pulse sequences, which represents greater possibilities for characterization of various CNS tissues than CT and is one of the advantages of MRI.

Standard or routine sequences used in the study of patients with brain metastases are T1, T2, and T2*. T1-weighted images are fundamental for detection of impairment and abnormalities of normal brain anatomy. Volumetric scanning 3DSPGR or VIBE allows to obtain T1-weighted high-resolution images with a 1.0 mm slice thickness and is currently used in routine diagnosis of metastatic brain lesions.

T2-weighted images are intended for visualization of edema and the presence of water in the tissues; SP T2-FLAIR suppresses the MR signal from free water (e.g., CSF) and better identifies hydration foci, demyelination, and hemorrhages in the brain tissue.

*T2-weighted images reflect the tissue magnetic susceptibility (Haacke et al. 2010, Kornienko and Pronin 2009a, b, c, d, 2010). The next step in the use of SP gradient echo became SWI (SWAN) sequences that are used to detect hemorrhages in metastatic brain lesions (Pronin et al. 2011; Dolgushin et al. 2012a, b; Haacke et al. 2010).

T1 MRI with intravenous contrast enhancement is often used in the diagnosis of neoplastic brain lesions, including metastases. MRI contrast agents (MRCA) are agents based on a paramagnetic material gadolinium (Gd), which shorten the T1 relaxation time. As a result, images of tissues that have accumulated MRCA will be bright in T1-weighted MRI. The concentration of gadolinium surrounded by a chelate providing stability of the product in the internal media of the human body may be from 0.5 mM/ml and 1.0 mM/ml in MRCA. During the standard procedure (neuro-oncology), a patient is administered 0.2 ml of the drug at the concentration 0.5 mm/ml/kg of body weight and 0.1 ml at the concentration 1.0 mM/ml. For a qualitative assessment of MRI signs of a tumor on tomograms, a subjective scale is generally utilized: the MR signal in the tumor can be isointense as compared to the brain matter on the contralateral side, hypointense or hyperintense. On T1-weighted images, MRI with contrast enhancement assesses only the degree of an increase in the MR signal intensity in the tumor (no enhancement, moderate and significant enhancement). A semiquantitative assessment of an increase in the relative tumor intensity on MRI with contrast enhancement (CE) is widely used in neuro-oncology, because of the simplicity of calculations and the information value of this parameter for neoplastic and nonneoplastic CNS lesions.

With contrast enhancement, even in the absence of clinical symptoms, metastases are detected in nearly 100% of cases (Kornienko et al. 2007). The use of intravenous bolus administration of MRCA allows to utilize the perfusion technique based on a decrease in the MR signal intensity on the T2 and T2* MRI in the diagnosis of brain metastases (Huisman and Sorensen et al. 2004).

Semiotics and differential diagnostic criteria for metastatic brain lesions, based on the results of the use of routine sequences (T1, T2, and T2-FLAIR) on the background of various doses of contrast agent, were discussed in sufficient detail in numerous publications (Konovalov et al. 1997a, b, c; Osborn 1994; Sze et al. 1998; Kornienko and Pronin 2008a, b, 2009a, b, c, d).

Standard MRI sequences can detect tumors and intratumoral changes (hemorrhage, necrosis) and assess the size of a peritumoral edema. In Т1-weighted image, metastases may have various signal characteristics with respect to the brain substance. If the tumor lesion has a lower signal (Fig. 9.1) than the intact brain substance, edematous brain tissue that is hypointense in this sequence makes it difficult to clarify the size, shape, and boundaries of the tumor. In case of a mild edema and a small metastasis (less than 1 cm in diameter), the latter may not be detected in T1-weighted image. According to our data, in T1-weighted image, metastases mainly (90%) have a hypo- and isointense MR signal in relation to the brain substance. A hyperintense signal within an MTS is less common (up to 5.5% of the cases) and is generally encountered in case of a hemorrhage (metastatic melanoma, renal cell carcinoma).

Some metastatic tumors have a number of pathognomonic imaging manifestations that allow to assume the nature of the primary tumor with a high probability, even based on routine investigations. Thus, the characteristic feature of melanoma in an MRI study is an increased signal in T1-weighted image before contrast enhancement, since melanin is characterized by paramagnetic properties. A heterogeneous and increased MR signal in many observations is usually associated with the presence of a hemorrhage in the tumor tissue.

On Т2-weighted images, metastases are characterized by an iso- or hypointense signal relative to the gray matter from the tumor stroma, an increased signal in the central necrotic area and an area of perifocal edema. Particularly noteworthy are colorectal adenocarcinoma metastases that were characterized by a marked hypointense signal in T2-weighted image in 83% of our cases (Fig. 9.2); some of them showed signs of moderate central necrosis; the presence of perifocal edema was noted in 100% of cases.

Small metastatic lesions without the use of CA can be detected on T2-weighted images by the presence of a peritumoral edema characterized by a hyperintense signal (Fig. 9.3). In the presence of a chronic or acute hemorrhage in the metastasis stroma, hypointense areas can be observed, while the tumor tissue has a heterogeneous MR signal. However, it must be kept in mind that detection of metastases may be difficult, especially in small tumors with mild perifocal edema of the brain substance.

T2-FLAIR sequence used in the standard MR protocol in metastatic brain lesions usually has two purposes: specification, along with T2 mode, of detected small tumor lesions without the use of a contrast agent and visualization of additional signal changes in the metastatic tissue structure. Most often, in this sequence, a metastatic lesion has a hypointense MR signal relative to the gray matter. A heterogeneous signal is always detected in the presence of a hemorrhage in the tumor tissue. If an MR signal from small metastases is isointense, with a mild perifocal edema of the brain substance, it is difficult to identify the boundaries of the lesion and sometimes of the metastasis itself (Fig. 9.4).

The use of T2-FLAIR sequence is also justified in the presence of solitary metastases. One of the most common primary brain tumors is glioblastoma . It is typically slightly hyperintense relative to the cortex in this sequence, which is regarded as one of implicit signs of differential diagnosis when comparing these tumors.

Contrast enhancement in MRI, as well as in CT, has a high diagnostic value. Structure of the lesion, spread and invasion of surrounding tissues, the number of lesions and hemodynamic characteristics of the tumor are identified best on the background of contrast enhancement. In case of brain metastases, the use of contrast agents is an obligatory link in the standard protocol of any diagnostic CT/MRI study. In literature, there is still debate over the possibilities and feasibility of the use of high doses of contrast agents for metastatic brain lesions. According to Sze et al. (1998), in 70 patients with negative results on MRI with a standard contrast agent dose out of 92 patients with confirmed or suspected metastatic brain lesions, administering a triple dose of the contrast agent did not help identify any additional lesion. Yuh et al. (1992), as well as other researchers, identified additional lesions after using a triple dose of the contrast agent in MRI only in a small number of cases (Akeson et al. 1995; Vogl et al. 1995; Tatsuno et al. 1996; Gasperini et al. 2000; Rowley et al. 2008; Attenberger et al. 2009).

A study using T1-weighted sequence with contrast enhancement can detect both large and pinpoint lesions of pathological CA accumulation not visualized with other types of contrast enhancement. However, according to Mintz et al. (2004), there is always a danger of a false-positive result. For example, in case of telangiectases or when the slice plane is perpendicular to the blood vessel, there is a possibility of erroneous interpretation of findings in favor of a nonexistent small metastasis. In such situations, it is advisable to use volumetric scanning programs. 3D FSPGR (T1-weighted sequence) allows to neutralize an increase in the signal from the blood flow; in some cases, constructing multiplane images or reformats allows to “remove” the course of the blood vessel and thus eliminate the seeming presence of a small metastatic lesion.

MRI with contrast enhancement as compared to CT allows to obtain the largest amount of diagnostic information regarding the tumor and conduct differential diagnosis between focal brain lesions similar in the standard modes by their visualization characteristics. Metastases, meningiomas, benign astrocytomas, lymphomas, and neuromas without contrast enhancement may look similar on CT and MRI. However, when there is a massive hemorrhage in the tumor, the use of contrast enhancement is often uninformative (Fig. 9.5).

Special attention was paid in our studies of patients with metastatic brain tumors to the specifics of CA accumulation by metastases of different origins. An MRI study with contrast enhancement determined the extent, nature, and time of CA accumulation and elimination from the area of interest. The main types of CA accumulation in the tumor tissue were identified based on the analysis of findings obtained: “target,” “blurred contour,” “in the form of a rim with clear contours,” “heterogeneous,” “annular,” “annular with a solid area,” and “homogeneous.” We will use this classification of CA accumulation hereinafter. The typical visualization features for each type of CA accumulation will be review below.

“Target”: CA accumulations as “blurred contour” and “in the form of a rim with clear contours” were combined in one group—both types are ring shaped with a “clearing” in the center, indicating the presence of tumor tissue decay in the middle area of the lesion. CA accumulation in the form of “blurred contour” is characterized by the presence on the periphery of the contrast enhancement of pointed areas (protrusions) that transit into the surrounding brain tissue without any clear contours. In another type of CA accumulation (“in the form of a rim with clear contours”), MR image of the lesion is annular but with a dense homogeneous halo with a clear, sharp boundary between the CA area and the brain substance (Fig. 9.6). Perifocal edema in metastases of these types of CA accumulation is very significant. Such metastases differ by different lesion sizes and various widths of a “ring” of CA accumulation. We observed CA accumulation in the form of a “target” in 36.8% of cases of breast cancer metastases (Dolgushin 2012).

A “heterogeneous” type is characterized by separate sites of CA accumulation with different sizes in different areas of the tumor (Fig. 9.7). In this type, in contrast to the two previous types of CA accumulation, clarification areas on the scan, corresponding to portions of necrotic tumor decay, are randomly located within the pathological focus. This type of CA accumulation is also observed in cases of hemorrhages in the tumor tissue, with the intensity of MR signal from blood clots sometimes exceeding that of the contrast-enhanced tissue. The extent of the perifocal edema varies and depends more on the characteristics of the tumor site and its size.

“A ring” is characterized by the accumulation of CA in the form of a thin, closed, annular rim, and we observed it in our clinical material in 15% of cases. This “ring,” as such, can have different shapes; therefore, this definition is quite arbitrary. No hemorrhages into the tumor tissue were observed in this type of CA accumulation. The signal from the central area of metastasis in all scan sequences was almost homogeneous. In solitary or even multiple brain metastases, lesions characterized on MRI scans by a similar type of CA accumulation most often have to be differentiated from brain abscesses. Tumors characterized by CA accumulation in the form of a “ring” almost completely lack a perifocal edema surrounding the brain substance (Fig. 9.8).

“Ring + tissue” in cases where a solid part of the tumor accumulating CA is adjacent to the annular “rim”: we defined this type of manifestation of metastases as “ring + tissue.” An annular cystic component is not in the center but is adjacent to the solid part of the tumor. There are sometimes areas of hemorrhages (in the solid portion). A perifocal edema in cases of such MR manifestation of tumors is quite significant (Fig. 9.9).

A “homogeneous” type of CA accumulation is the most frequent MRI picture of the tumor lesion (30.8%). It is characterized by uniform accumulation of contrast agent in metastases represented by a solid lesion, while the degree of CA accumulation may be different. The brain edema in this type of MRI manifestations of the tumor is significant (Fig. 9.10).

Distribution of observations based on the accumulation characteristics of contrast agent in brain metastases is shown in Table 9.1.

There is no significant relationship between the type of CA accumulation and abnormal structure of the primary tumor. Metastases of different etiologies may be contrasted in the form of a “target.” The same is applicable to other CA accumulation patterns. Differences in CA accumulation by metastases, in our opinion, are due to, first of all, their size, duration of existence, intensity of the tumor growth, and metabolic activity of the tumor tissue, which manifests by the absence or presence of areas of necrosis, decay, and bleeding in the abnormal focus. The confirmation of this can be seen in one of our cases, when, in multiple brain metastases, a few different types of CA accumulation were found, as well as the detection of the same type of contrast in metastatic tumors that differed in their histogenesis (Fig. 9.11).