Neuroradiological Diagnostic Imaging

Standard MRI

In ischaemic stroke, the diagnostic role of conventional MR is confined to the subacute and chronic phases, since in the very early hours from the event the changes in interstitial water content (free water) induced by Na+/K+ pump alterations are not yet such as to affect the signal in T2-weighted (FSE or FLAIR) sequences, thus yielding a negative MR examination in the hyper-acute phase (Fig. 14.1).

Also in MR studies, one of the first signs of ischae-mia secondary to arterial occlusion is a signal change in the lumen of the blocked vessel. Whereas in SE sequences vessels normally present a signal void due to arterial and/or turbulent flow (Fig. 14.2), occluded vessels exhibit a characteristic hyperintensity, especially in FLAIR sequences, with an accuracy that is comparable to that of MRA [6, 7].

Even though the cytotoxic oedema does not give rise to signal changes, it can be indirectly detected in cortical areas through gyral swelling, sulcal effacement and a loss of grey-white matter interface definition. Contrast-enhanced sequences, which are not employed routinely, show vascular enhancement due to the slower flow in the occluded or tributary vessel, sometimes associated with tissue enhancement due to local hype-raemia or extravasation of contrast agent through the disrupted endothelium. MR signal changes become evident in the acute phase, when the vasogenic oedema induces hyperintensity in long TR (FSE T2 and FLAIR) sequences (Fig. 14.3) and contrast-enhanced scans may depict a pathological meningeal enhancement [8]. In the subacute phase (3 -14 days), the signal changes are more marked due to the increasing mass effect and manifest as a signal increase in T2 FSE and FLAIR sequences and hypointensity in T1 SE. On contrast-enhanced scans, enhancement of the infarcted area, which can persist for more than 2 months, is due to the recanalization of the occluded vessel, the opening of collateral circles (luxury perfusion) and BBB changes. In 20% of cases, rupture of the vascular endothelium following thrombolysis may result in haemorrhage. This phenomenon appears as hypointense foci in T2 and is best seen in GE sequences [9]. In the chronic phase, a very hypointense „haemosiderin tattoo" due to even slight earlier bleeding is consistently detected in all sequences [2].

Chronic-phase MR findings reflect the morphostructural changes induced by the progressive shrinking of the lacunae, which have a cerebrospinal fluid-like content, while the hyperintensity of the adjacent brain parenchyma (particularly evident in FLAIR sequences) is due to reparative gliosis (Fig. 14.4). In this phase,

Fig. 14.1. Small hyperacute stroke. The standard MR study (T2 FSE) is negative (a). The DWI image shows a hyperintense left subcortical parietal ischaemic focus (b)

Fig. 14.2. Combined study with morphological MR sequences in the hyperacute phase. The brain parenchyma does not exhibit ischaemic foci on the standard study (T2 FSE) (a); note the flow void in the intracavernous tract of the left internal carotid artery. This finding is confirmed by the 3D TOF MRA study with coronal reconstruction (b)

Fig. 14.2. Combined study with morphological MR sequences in the hyperacute phase. The brain parenchyma does not exhibit ischaemic foci on the standard study (T2 FSE) (a); note the flow void in the intracavernous tract of the left internal carotid artery. This finding is confirmed by the 3D TOF MRA study with coronal reconstruction (b)

signs of Wallerian degeneration of axons (and their myelin sheaths) originating from the infarcted area must be sought. Anterograde axon degeneration, which initially induces degradation of the protein component of myelin while comparatively sparing its lipid compo nent (low signal in FSE T2 sequences), and afterwards reparative gliosis, is depicted on standard MR only in very late phases, i.e. when the axon degeneration has become irreversible. Again, earlier detection of these phenomena can be obtained with DWI [9].

Fig. 14.3. Combined study with morphological MR sequences in the acute phase. Vast right cerebel-lar stroke. Right cerebel-lar hypodense area in T1 FSPGR (a); ill-defined right hemicerebellar hyperintense area in T2 FSE (b). Occlusion of the right vertebral artery in 3D TOF MRA (c)

MR Diffusion

DWI is the most sensitive technique to diagnose hyper-acute-phase brain ischaemia (Fig. 14.1). Based on the diffusion of water molecules in the cell compartment, their random movement induced by thermal energy can be measured using conventional SE echo-planar sequences acquired with specific weighting. These sequences are sensitive to the movement of H2O molecules and demonstrate the changes in diffusion induced by pathological events in the form of images and numerical values. In hyperacute ischaemia, the histo-

Fig. 14.3. Combined study with morphological MR sequences in the acute phase. Vast right cerebel-lar stroke. Right cerebel-lar hypodense area in T1 FSPGR (a); ill-defined right hemicerebellar hyperintense area in T2 FSE (b). Occlusion of the right vertebral artery in 3D TOF MRA (c)

Mrt Hstadium
Fig. 14.4. Lacunar sequelae of a left capsular ischaemic stroke in FLAIR (a) and T2 FSE (b)

pathological injury is the cytotoxic oedema; the H2O molecules trapped in the cell thus exhibit an impaired diffusion, which is detected in a few minutes as a signal increase in the pathological tissue [10-12].

DWI techniques are sensitive as well as specific (90% and 99%, respectively); these two parameters are directly proportional to the time since disease onset. A negative DWI study does not however exclude a diagnosis of ischaemia. Not all patients with a typical picture of stroke also display an altered DWI signal; this may be due to complete recovery from a TIA, to a non-ischaemic event, or to symptomatic hypoperfusion [13]. Obviously, the DWI studymay also have preceded the establishment of an infarcted area, or the lesion maybe very small and lie in areas especially difficult to investigate with this method (temporal regions, posterior cranial fossa).

Unlike standard MR, where the hyperintensity of the ischaemic area in long TR sequences corresponds with the expansion of the vasogenic oedema, DWI enables precise evaluation of the injured tissue because the signal hyperintensity peaks within 24 h of clinical onset, and never later. In addition, DWI sequences afford separate visualization of the acute ischaemic area, characterized by strongly reduced diffusion, from the peripheral area, where the apparent diffusion coefficient (ADC) is less affected (although PWI techniques are even more informative; see below) and the tissue damage may be reversed. This is the ischaemic penumbra, which has not sustained a stroke proper, but exhibits the predisposing physiopathological conditions for a new stroke (energy deficit), making it a high-risk area in the subacute phase. Adequate reperfusion often results in functional recovery of the ischaemic penumbra [12].

Another advantage of DWI over standard MRI is that, in patients with multifocal leukoencephalopathy, it allows the identification of the ischaemic lesions responsible for the active symptoms.

MR Perfusion

PWI techniques study changes in blood flow at the level of the microcirculation using ultrafast sequences with a bolus of paramagnetic contrast medium (gadolinium; Gd) [15]. In normal perfusion and intact BBB conditions Gd, though remaining confined to the intravascu-lar space, induces a reduction in T2 signal both in vessels and in the brain parenchyma. In a hypoperfused area (for instance one due to a vascular occlusion), the signal reduction is delayed or attenuated (due to magnetic susceptibility) because of the diminished flow. Since the signal reduction correlates directly with Gd concentration, and thus with cerebral blood volume (CBV), parametric CBV maps of the areas with reduced signal intensity can also be generated.

In stroke patients, the main role of PWI studies is to identify the ischaemic penumbra in the acute phase. Studies of the relationship between cerebral blood flow (CBF) and neuronal disruption have evidenced that there is a short interval related to CBF changes, where neurons, though no longer efficient, are still viable and can be rescued with a suitable therapy. The extension of this area depends both on the duration of the ischaemia and on its entity, because even mild ischaemia, which does not necessarily cause neuronal damage, may induce irreversible injury if protracted.

Combined Diffusion and Perfusion Studies

DWI and PWI studies are more informative in combination than singly, especially in predicting clinical evolution and outcome, and thus in guiding therapy [10, 16-18].

Six different patterns can be identified using combined studies:

1. The area exhibiting reduced perfusion, which also includes the penumbra, is larger than the one exhibiting reduced diffusion (Fig. 14.5). A PWI>DWI mismatch is the most common pattern (55 - 77 % of cases), especially in the hyperacute phase. From the point of view of clinical evolution, early PWI scans depict the maximum size attainable by the infarcted area and, in absence of further vessel occlusion or closure of collateral circles, the worst clinical outcome

2. Similar pathological areas with both methods (Fig. 14.6)

3. A smaller pathological area on PWI (PWI<DWI mismatch)

4. Presence of diffusion, not perfusion, deficits

5. Presence of perfusion, not diffusion, deficits (usually associated with a transient neurological deficit)

6. Negative diffusion and perfusion studies despite an evident clinical alteration

Combined studies can be useful to predict clinical evolution, assess prognosis and evaluate the response to therapy [1,19]. Patterns #1 and #5 are managed with reperfusion treatment using fibrinolytic agents, the others with neuroprotective drugs.

MR Spectroscopy

MR spectroscopy enables non-invasive in vivo study of some phases of brain metabolism. It is based on the same principles as conventional MR, except that it envisages signal processing during and after sequence acquisition. Whereas in standard MR the signal intensity is the sum of the signals from all the hydrogen-contain-

Spectroscopy Lip Lac

the same machine as standard MRI using appropriate software. It records signals from N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and phosphocrea-tine (PCr), myo-inositol (ml), lactate (Lac), lipids (Lip), glutamine and glutamate (Glx). These metabolites are found in nerve cells at greater than millimolar (mM) concentrations and have spectra at known positions, which are expressed as parts per million (ppm).

NAA, which is found almost exclusively in the CNS in neurons, and to a lesser extent in some glial cell precursors, is therefore considered as a neuronal marker. Since it is almost equally present in white and grey matter, it can also be considered an axonal marker. Its highest peak in adults is at 2 ppm.

Cho, whose peak is found at 3.22 ppm, contains lipids like phosphocholine and glycerophosphocholine; it therefore reflects the cellular turnover and is considered as a membrane marker.

Cr and PCr exhibit a single peak at 3.02 ppm that pools the signal from the high-energy phosphates involved in the energy metabolism. Since its peak is stable also in pathological conditions, it is used as a control value.

Myo-inositol, considered as a specific glial marker, is found at 3.3 - 3.6 ppm.

When present, Lac exhibits a doublet peak at 1.32 ppm. It reflects the production of energy in conditions of altered oxygen supply, a situation that takes place when a partial vessel occlusion activates the enzymatic pathway, which leads to anaerobic glycolysis. Lactate can also accumulate due to infiltration of Lac-containing macrophages, or because it has remained trapped and has not been removed.

Lip, which are mainly found in necrotic processes, resonate at 0.8,1.2, and 1.5 ppm.

Adc Dwi Mismatch
Fig. 14.5. Combined functional study with DWI < PWI mismatch. DWI (a), ADC map (b), regional CBV map (c). Note that the hypoperfused area (c) is broader on PWI (a, b)

ing molecules in a given volume, in spectroscopy the signal from a given nucleus is separated into its chemical components. The physical principle underpinning the change in the resonance frequency of nuclei is the chemical shift. This is influenced by the magnetic field generated by the cloud of electrons that surrounds the nuclei as well as by the clouds of electrons of nearby atoms, which interact with the main magnetic field. An atom is thus subject to different chemical shifts as a function of the molecule in which it is found, thus enabling identification of the molecule containing it. Hydrogen spectroscopy is currently the most widely used of these techniques, because it can be performed with

Fig. 14.6. Combined functional study without mismatch (DWI = PWI). Vast right parieto-occipital ischaemic stroke in the hyperacute phase. Ischaemic multifocal leukoencephalopathy without recent ischaemic lesions in T2 EPI (a). Marked hyperintensity of the infarcted area in DWI (b). Right parietal-occipital signal hyperintensityin PWI (c) indicating reduced perfusion ofthe ischaemic area of similar extension as the one shown in DWI. The spectroscopic single-volume short-TE image shows a marked reduction in the NAA, Cho and Cr peaks, and a Lac peak at 1.3 ppm (d)

Fig. 14.6. Combined functional study without mismatch (DWI = PWI). Vast right parieto-occipital ischaemic stroke in the hyperacute phase. Ischaemic multifocal leukoencephalopathy without recent ischaemic lesions in T2 EPI (a). Marked hyperintensity of the infarcted area in DWI (b). Right parietal-occipital signal hyperintensityin PWI (c) indicating reduced perfusion ofthe ischaemic area of similar extension as the one shown in DWI. The spectroscopic single-volume short-TE image shows a marked reduction in the NAA, Cho and Cr peaks, and a Lac peak at 1.3 ppm (d)

Finally, Glx exhibits peaks at 2.1-2.5 and 3.6-3.8 ppm, and pools the signal from neurotransmitters such as glutamate and glutamine.

In CNS ischaemic disease, spectroscopy can be used for the early detection and characterization of ischae-mic lesions (Fig. 14.6), to monitor the response to therapy, and especially to distinguish the infarcted area from the ischaemic penumbra [20-22]. The necrotic area is characterized by a reduction in NAA (50 % over the first 6 h), whereas the penumbra displays an increased Lac peak without significant changes in NAA [23]. A marked NAA reduction and a strong Lac increase in the acute phase predict an unfavourable outcome.

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