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Diagnosis of Thin-Cap Fibroatheromas by a Self-Contained Intravascular Magnetic Resonance Imaging Probe in Ex Vivo Human Aortas and In Situ Coronary Arteries

Jacob Schneiderman, MD^_*, Robert L. Wilensky, MD, FACC^,_*, Assaf Weiss, BSc, Eitzek Samouha, BSc, Lev Muchnik, BSc, Malca Chen-Zion, PhD, Mordechay Ilovitch, PhD, Erez Golan, MSc, Aharon Blank, PhD, Moshe Flugelman, MD, Yosef Rozenman, MD, FACC^|| and Renu Virmani, MD, FACC^¶

^_* Department of Vascular Surgery and Gottesdiener Vascular Biology Laboratory, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
TopSpin Medical Israel, Lod, Israel
Department of Cardiology Carmel Hospital, Haifa, Israel
^|| Wolfson Hospital, Holon, Israel
^¶ Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC

View larger version (58K): [in a new window]   Figure 1 Schematic representation of the magnetic resonance imaging (MRI) catheter within an artery. (Left) The artery is shown in the longitudinal axis with juxtaposition of the MRI catheter close to a segment of the arterial wall containing a lipid-rich core. The slice thickness of the MRI measurement is 2 mm in length. (Right) Cross section of the artery is shown with the catheter in close proximity to a radial 60° section containing two evaluated detection bands within the field of view (0 to 100 µm and 100 to 250 µm). The catheter is connected to its interface control unit and the imaging console.

View larger version (50K): [in a new window]   Figure 2 Depiction of the magnetic resonance imaging (MRI) catheter with imaging areas superimposed on a cross section of a human coronary artery (left). Interrogation of the arterial wall is in four quadrants, each comprising a field of view. A single field of view is denoted by the white arrowhead. The MRI diagram (right) displays the lipid fraction in each quadrant assessed by the catheter. In this particular illustration, an increased lipid concentration is noted only in quadrant 3, as it displays yellow. Quadrants 1, 2, and 4 are shown in blue, indicating a low lipid content or increased fibrous content.

View larger version (83K): [in a new window]   Figure 3 Photomicrographs of a thin cap fibroatheroma in a human coronary artery. (A) An old rupture of the fibrous cap overlying a large necrotic core (NC) is shown (arrow) (section stained with hematoxylin-eosin). (B) Adjacent section stained with oil red O to demonstrate the presence of lipids within the arterial wall. Note that increased staining is noted throughout the lesion both in the area of the NC as well as the fibrous cap (box). (C, D) Higher magnifications of boxed areas seen in A and B. Panel C shows foam cells within the thin fibrous cap stained with hematoxylin-eosin, whereas panel D shows oil red O staining. This artery was correctly identified as a thin cap fibroatheroma by magnetic resonance imaging.

View larger version (15K): [in a new window]   Figure 4 Lipid fraction assessed by magnetic resonance imaging in three homogeneous components of aortic atherosclerotic lesions. The fibrous component showed the least amount of lipid (13 ± 13%), significantly less than that obtained from areas rich in foam cells (46 ± 12%, p < 0.0001) and necrotic cores (69 ± 14%, p < 0.0001 vs. fibrous plaque, p < 0.001 vs. foam cells).

View larger version (88K): [in a new window]   Figure 5 Examples of four aortic specimens and corresponding MRI displays. (A to D) Movat’s pentachrome-stained samples. (E to H) Adjacent sections stained with anti-CD-68 (brown) to identify areas rich in macrophages and lipid. (I to L) Corresponding intravascular magnetic resonance imaging (MRI) displays. Arrows indicate the location of MRI interrogation. (A, E) Thick-cap fibroatheroma with the fibrous cap at the site of MRI measurement 120 µm in thickness (arrow). The CD-68 photomicrograph (E) reveals that an increased macrophage concentration is observed primarily in the deep layer. The corresponding MRI display (I) demonstrates the presence of lipid in the 100 to 250 µm deep layer (yellow), whereas the superficial 0 to 100 µm segment has a low lipid content, thus the MRI read-out is blue. (B, F) Ulcerated plaque; the interrogated necrotic core is near the surface (arrow). There are hemorrhagic areas within the necrotic core, and the corresponding CD-68–stained section (F) shows increased staining in the necrotic core. The corresponding MRI display indicates a high lipid content in both the superficial and deep bands (0 to 100 µm and 100 to 250 µm). (C, G) Normal aortic wall devoid of plaque. No anti-CD-68 staining is observed in panel G. The MRI interrogation (K) showed a high fibrous content and is devoid of lipid (blue) in both bands. (D, H) Thin-cap fibroatheroma (cap 50 µm in thickness) with the cap infiltrated by foam cells and a deeper necrotic core observed in the histologic section, as well as in the corresponding CD-68–stained section (H). The MRI display shows a high lipid content within both bands (L). Original magnification is x20. The 100-µm bar is for the MRI images, whereas the 250-µm bar is for the Movat’s and CD-68–stained sections.

View larger version (112K): [in a new window]   Figure 6 The magnetic resonance imaging (MRI) scan demonstrates excellent correlation with histology. Coronary angiography, MRI, and histologic cross sections of three intermediate coronary lesions are shown. An arrow on the angiogram marks the site of interrogation. The corresponding MRI is shown in the second column, whereas corresponding histologic sections of the interrogated sections are shown in the third and fourth columns (Movat’s pentachrome and anti-CD-68 antibody staining, respectively). (A) Thin-cap fibroatheroma (left to right) in the proximal left anterior descending artery; the MRI display shows the presence of a high lipid content within three quadrants (2 to 4). Quadrant 1 has little lipid within the wall, as indicated by the lack of foam cells by Movat’s staining or macrophages by CD-68 staining. Quadrant 2 has moderately increased lipid concentrations, as noted by an approximate lipid fractional index of 60%. Quadrant 3 has increased lipid only in the deep layer, whereas quadrant 4 has high lipid fractional indexes (±100%) within the superficial and deep layers. Approximately 75% of the arterial circumference is lipid-rich. The MRI display corresponds well with subsequent histology, as the Movat’s section shows a large necrotic core (*) and a thin fibrous cap, and the adjoining immunohistochemical staining shows markedly positive staining for CD-68 in the area corresponding to quadrant 4 of the MRI display. (B) Thick-cap fibroatheroma in the right coronary artery. The MRI display shows no lipid content within the superficial layer (blue); however, a mild degree of increased lipid concentration is observed within the deep band (>100 µm from the lumen in quadrant 5 only. The lipid fractional index is about 50%. The corresponding histologic section shows a thick-cap fibroatheroma with a small, deep necrotic core (+), confirmed by the anti-CD-68 staining, corresponding with the MRI image. Because there is little to no lipid within the superficial layer, this lesion is considered a thick fibroatheroma. (C) Stable lesion. A mild stenosis by angiography is seen in the intermediate branch of the left coronary artery. The MRI display of the lesion shows no increased lipid concentration in the shallow or the deep bands of any quadrant, indicating the presence of a fibrous lesion (hence, blue display). This diagnosis was confirmed by histology as adaptive intimal hyperplasia, and the corresponding anti-CD-68 staining was negative for foam cells or a necrotic core.