Manganese-enhanced MRI visualizes V1 in the non-human primate visual cortex

Abstract

MRI at 7 Tesla has been used to investigate the accumulation of manganese in the occipital cortex of common marmoset monkeys (Callithrix jacchus) after administering four fractionated injections of 30 mg/kg MnCl(2) . 4H(2)O in the tail vein. We found a statistically significant decrease in T(1) in the primary (V1) and secondary (V2) areas of the visual cortex caused by an accumulation of manganese. The larger T(1) shortening in V1 (DeltaT(1) = 640 ms) relative to V2 (DeltaT(1) = 490 ms) allowed us to robustly detect the V1/V2 border in vivo using heavily T(1)-weighted MRI. Furthermore, the dorso-medial (DM) and middle-temporal (MT) areas of the visual pathway could be identified by their T(1)-weighted enhancement. We showed by comparison to histological sections stained for cytochrome oxidase (CO) activity that the extent of V1 is accurately identified throughout the visual cortex by manganese-enhanced MRI (MEMRI). This provides a means of visualizing functional cortical regions in vivo and could be used in longitudinal studies of phenomena such as cortical plasticity, and for non-destructive localization of cortical regions to guide in the implementation of functional techniques.

Figure 1

A representative T1 map in a marmoset following four injections of 30 mg/kg MnCl2·4H2O showing the regions of interest (ROIs) used to measure the values in Table 1. (V1 = gray matter in V1, WM = white matter proximal to V1, V2 = gray matter in V2).

Figure 2

A comparison of contrast in manganese-enhanced MRI in the marmoset occipital cortex versus staining for cytochrome oxidase (CO) activity. Upper Left: Slice from an in vivo T1-weighted coronal MRI in the occipital cortex of a marmoset following systemic injections of manganese. The in-plane image resolution and slice thickness are 167 µm. The cerebellum, brainstem, skull, and surrounding tissue have been masked in the MRI during post processing. The contrast to noise ratio (CNR) between V1 and V2 is 1.4 (CNR = magnitude signal intensity in V1 > magnitude signal intensity V2 / standard deviation of the noise in the image background). Lower Left: An image made prior to manganese injections using the same MP-RAGE pulse sequence, but with a shorter inversion time to maximize global image contrast in the presence of the longer, endogenous T1s. Upper Right: A corresponding 40 µm thick histological section stained for cyctochrome oxidase (CO) activity. (I–III, IV, V–VI denote cortical layers, WM = white matter). Note the strong staining in layer IV in the CO section that defines the extent of V1. The arrows denote the V1/V2 border. The T1 enhancement in the MRI corresponds to V1 identified on the CO section with the strongest layer-specific enhancement occurring in the location of layer IV.

Figure 3

The extent of V1 is identically identified across the occipital cortex with manganese-enhanced MRI and CO staining. 167 µm in vivo T1-weighted MRI slices and corresponding 40 µm thick CO sections through the occipital cortex. The area of T1 enhancement in the MRI slices corresponds well to V1 as defined by the dark staining in layer IV in the CO sections. The MRI slices are from a 3D MRI in a single marmoset. Slices begin 2.0 mm anterior to the occipital pole and continue in the anterior direction with 0.84 mm spacing. The CO slices are from four marmosets. (P = posterior, A = anterior).

Figure 4

a: The V1/V2 border identified on the surface of the occipital cortex by manganese-enhanced MRI. Left: A volume rendering of a T1-weighted 3D MRI in a marmoset following systemic manganese injections. Note that the 3D MRI only covered the occipital cortex. The data is displayed using the >Voltex> rendering function in Amira. For this, the MRI volume was masked to only include cortical tissue. Each voxel in the the data volume was assumed to emit and absorb light. The amount of emitted light and the amount of absorption was determined from the MRI magnitude data by using a colormap. This image thus intuitively shows the strong T1 enhancement in V1. There is also lighter enhancement in regions corresponding to the location of the middle temporal (*) and dorsomedial (**) areas. Right: A surface rendering of the marmoset brain shown for localization. The dotted line shows the extent of the 3D image used to generate the Left figure. (P = posterior, A = anterior, D = dorsal, V = ventral). b: Coronal slice from the in vivo T1-weighted MR image used to created Figure 4a showing light enhancement in the middle temporal (*) and dorsomedial areas (**).

Figure 4

a: The V1/V2 border identified on the surface of the occipital cortex by manganese-enhanced MRI. Left: A volume rendering of a T1-weighted 3D MRI in a marmoset following systemic manganese injections. Note that the 3D MRI only covered the occipital cortex. The data is displayed using the >Voltex> rendering function in Amira. For this, the MRI volume was masked to only include cortical tissue. Each voxel in the the data volume was assumed to emit and absorb light. The amount of emitted light and the amount of absorption was determined from the MRI magnitude data by using a colormap. This image thus intuitively shows the strong T1 enhancement in V1. There is also lighter enhancement in regions corresponding to the location of the middle temporal (*) and dorsomedial (**) areas. Right: A surface rendering of the marmoset brain shown for localization. The dotted line shows the extent of the 3D image used to generate the Left figure. (P = posterior, A = anterior, D = dorsal, V = ventral). b: Coronal slice from the in vivo T1-weighted MR image used to created Figure 4a showing light enhancement in the middle temporal (*) and dorsomedial areas (**).

Figure 5

An ex vivo coronal MR image of a fixed marmoset brain showing the position of the lateral ventricles in the occipital lobe. Gray matter surrounding the calcarine fissure in the occipital cortex is supplied with Mn2+ ions via a CSF-brain uptake route. (GM = gray matter, CF = calcarine fissure, pos LV = posterior horn of the lateral ventricle, WM = white matter).