Clinical Applications of MRI One

7AHP0203
Discuss the current clinical Applications of MRI, with reference to two clinical situations
Introduction
MRI is an excellent imaging modality; in particular it is praised for superior soft tissue contrast and resolution (Westbrook, Roth & Talbot, 2005). It has many clinical uses and has established itself as the gold standard in the imaging of several pathologies (The royal college of Radiologists (RCR), 2007). Nevertheless, MRI has limitations, having a propensity to numerous imaging artefacts and a reliance upon an abundance of mobile hydrogen protons to provide adequate signal-to-noise (SNR) (McRobbie, Moore, Graves & Prince, 2003). There are also safety concerns, owing to the powerful magnetic field, time-varying gradient magnetic fields and radiofrequencies used to excite the hydrogen protons (De Wilde, Granger, Price & Renaud, 2007; Medicines and Healthcare products Regulatory Agency (MHRA), 2007a).
MRI is also an expensive and precious commodity that is often time consuming and so its clinical use has to be carefully rationed to those cases where it is best suited (RCR, 2007). Although the clinical decision to send a patient for MRI lies with the referring clinician, the radiology department must scrutinize all requests to ensure that the scan is justified and in the best interests of the patient (Department of health, 2000; RCR, 2007). MRI Radiographers must therefore have a comprehensive understanding of both MRI safety and the diagnostic value of MRI in different clinical scenarios (Westbrook & Talbot, 2009). In addition, a sound knowledge in MRI science and application enables an MRI radiographer to select appropriate protocols, and manipulate any necessary parameters, to accommodate different patient requirements, as they present themselves.
This essay looks at two clinical scenarios, discussing the diagnostic value of MRI in each case, relative to other imaging modalities and a consideration of the risk-benefit ratio in their individual circumstances.
1) A 50-year-old male with acute loss of consciousness, of unknown cause. There is no apparent trauma, but an uncertain history.

Differential Diagnoses
Gould (2006) explains that a person’s level of consciousness is determined by the reticular activating system (RAS) in the brainstem, and the cerebral cortex. In order to cause unconsciousness, supratentorial lesions would need to be bilateral and diffuse (Bateman, 2001). Unilateral cerebral mass lesions can also cause coma if they cause downward herniation of the brain and secondary brainstem compression (Epstein, Perkin, Cookson & Watt, 2008). Conversely, relatively discrete lesions of the brainstem can have a significant effect on the RAS, and cause altered consciousness (Gould, 2006).
Beck, Souhami, Hanna and Holdright (2003) describes several disorders that can result in diffuse cortical dysfunction. These include metabolic disease, drugs, anoxic ischaemia, infection, vascular disease, trauma and epilepsy. Pathologies that result in dysfunction of the RAS include both supratentorial and infratentorial focal lesions (Beck et al., 2003). Epstein et al. (2008) state that supratentorial masses that induce coma tend to be vascular rather than tumour, whereas infratentorial lesions have a wider differential to include infarction, tumour and haemorrhage.
Initial assessment should include patient history, physical examination and neurological assessment that could suggest some underlying cause (Bateman, 2001). Focal signs (such as paralysis) would suggest a focal lesion – for example intracranial haemorrhage. Meningeal irritation may be detected in the unconscious patient by abnormal nick stiffness (Epstein et al., 2008) and is suggestive of meningitis or subarachnoid hemorrhage (Bateman, 2001), both of which can be investigated with lumbar puncture provided there are no clinical signs of raised intracranial pressure (Beck et al., 2003). Diabetic coma may be suspected from the clinical picture and confirmed by blood and urine analysis. Drug overdose may be suspected where skin puncture wounds, or empty drug vessels are evident (Beck et al., 2003).
Purpose of imaging
In this acute setting, brain imaging may be required to show an underlying cause of the LOC and direct treatment. As the differential diagnosis is wide, it would be pertinent to rule out intracranial bleeds, infarction, tumour and infection. The National Institute for Health and Clinical Excellence (NICE, 2008) sets out guidelines of how imaging should be used in cases of suspected stroke and states that early imaging can significantly improve patient outcomes because it permits early thrombolysis in ischaemic stroke, a treatment that is contraindicated in haemorrhage (Latchaw et al., 2009). Brain tumours may require urgent surgical intervention if they are compressing the brain stem. Infections such as abscesses may require drainage or appropriate antimicrobial therapy (Gould, 2006). For these reasons, imaging should be performed as soon as possible.
Diagnostic Value of MRI
MRI is excellent at imaging the brain – mostly owing to its superior ability to demonstrate grey-white matter differentiation and pathology (Coles, 2007; Koretsky, 2004). It is also the preferred imaging modality for investigating posterior fossa lesions (RCR, 2007; Coles, 2007). A variety of sequences are typically employed to depict the structural anatomy and to best highlight any pathology (Weiss, Galanaud, Carpentier, Naccache & Puybasset, 2007).
T1 sequences will show the anatomical brain clearly and provide a baseline prior to gadolinium contrast if required (Westbrook et al., 2005). Indications for gadolinium contrast include suspected tumours and infection to help distinguish between lesion and oedema (Bellin, 2006). T2-weighted sequences show most pathologies as high signal due to an oedema process or demyelination (Koretsky, 2004). Fluid attenuated inversion recovery (FLAIR) scans are of particular value if the pathology resides in the periventricular regions as the sequence nulls the signal from cerebrospinal fluid (CSF), while other fluids remain bright (figure 1)(Coles, 2007). Weiss et al. (2007, p 2) describes FLAIR as the “primary sequence in neuroradiology” owing to its ability to demonstrate subarachnoid or intraventricular haemorrhage, brain contusion and oedema, and their comorbidities such as brain herniation or ventricular dilation. However, Latchaw et al. (2009) report that it is possible to obtain false positives, with respect to subarachnoid haemorrhage due to cerebrospinal fluid turbulence.

With reference to intracranial bleeds, gradient echo (GE) sequences are particularly sensitive to blood products, as the gradients are unable to compensate for the magnetic susceptibility properties of haemosiderin (figure 2) (Coles, 2007). Latchlaw et al. (2009) report that in blind-ended studies, GE MRI demonstrated intracranial haemorrhage at least as well as CT, the current gold standard.
Where acute ischaemia is suspected, diffusion weighted imaging (DWI) and apparent diffusion co-efficient maps (ADC) have been found to be the most sensitive and specific imaging tool (RCR, 2007; Weiss et al., 2007; Latchaw et al., 2009). Early infarction shows as high signal on DWI and low signal on ADC maps (Figure 3), due to the influx of water into the restricted intracellular compartment (Coles, 2007). This can be demonstrated within minutes of the infarction and a sensitivity of nearly 100% can be achieved after 2 hours post infarction (Mukherji, Chenevert & Castillo, 2002). If infarct is detected, MR angiogram (MRA) can be performed quickly and simply, with no need for contrast agent injection by utilizing a TOF (time-of-flight) sequence (RCR, 2007). However, TOF sequences have some disadvantages such as in-plane flow saturation (Westbrook et al., 2005). MR perfusion can provide vital information regarding the viability of tissue prior to surgery, as necrotic brain cells are unable to regenerate (Latchaw et al., 2009; Coles, 2007; Koretsky, 2004). However, this requires a bolus injection of gadolinium, and one must consider the potential risks of NSF and allergy (Gauden, Phal & Drummond, 2010; MHRA, 2007b).
If tumour is suspected, RCR (2007) state that MRI is more sensitive than CT in the early stages especially in posterior fossa lesions. In addition, Sanghvi (2009) highlights the ability of DWI and ADC maps to further aid diagnosis in distinguishing high-grade necrotic tumour, from abscess. Both will show on CT and MRI as a ring-enhancing lesion, but only an abscess will demonstrate restricted diffusion at its center.
MR spectroscopy may provide additional information about cerebral metabolism, or tumour characterization, which may be of use in predicting outcome (Coles, 2007; Sanghvi, 2009). However, MRS is time consuming, has poor spatial resolution, and is unlikely to be used in the routine work-up of the acutely unconscious patient (Coles, 2007).
Safety Concerns
In this unconscious patient with unclear history, it is difficult to ascertain whether they are safe to have an MRI. The main clinical concerns would include pacemakers and other implantable devices, intraorbital foreign bodies (IOFB), and neurovascular clips (MHRA, 2007a; Gauden et al., 2010). Many of these could be ruled out with a combination of medical history, physical examination and x-ray examination (where appropriate). This is time consuming and would not be suitable in the acute setting – imaging should not delay urgent medical treatment (RCR, 2007). In addition to this, an unconscious patient may require close monitoring or mechanical ventilation, both of which are difficult to manage in the MRI suite (Coles, 2007; Weiss et al., 2007).
Alternative Imaging Modalities
CT is useful in the acute unconscious patient as it can be performed quickly, is relatively available and can demonstrate many pathologies (Coles, 2007; RCR, 2007). CT’s main limitation is in the posterior fossa, where beam-hardening effects can obscure the soft tissue (Coles, 2007). When compared to MRI, CT is also inferior at grey-white matter differentiation and showing white matter abnormalities.
CT can differentiate between ischaemic and haemorrhagic stroke (figure 4) (RCR, 2007) and is therefore indicated whenever a cerebrovascular accident is suspected (NICE, 2008). However, early signs of ischaemic infarction such as loss of grey-white matter differentiation are quite subtle and Latchlaw et al. (2009) report sensitivity as low as 31% for stroke in the early stages, increasing to 82% at 6 hours (outside of the therapeutic window for thrombolysis). If infarct is detected/suspected, CT angiography and perfusion are good alternatives to MRA and MR perfusion and provide similar information indicating level of infarction and tissue viability (Coles, 2007). CT perfusion involves sequential acquisition and hence has higher radiation doses when compared to standard CT brain scans (Coles, 2007). Additionally, CT perfusion requires an infusion of iodinated contrast agent, which is contraindicated in patients with poor renal function or known allergy (Armstrong, Wastie & Rockall, 2009).

SPECT (Single photon emission computer tomography) is an alternative to CT/MR perfusion and can demonstrate blood flow through the brain; however the images produced have low resolution and do not provide quantitative measurements (Coles, 2007). Alternatively, PET (Positron Emission tomography) is able to assess perfusion quantitatively and demonstrate cerebral metabolism but is not universally available and its use is currently more in the research field (Coles, 2007).
In the case of a subarachnoid haemorrhage, CT is described as the ideal investigation provided it is performed early (Latchlaw et al., 2009). Al Shahi et al. (2006) state that CT only miss 2% of SAH if scanned within 12 hours, increasing to 7% by 24 hours. After around 10 days, the blood is resorbed and undetectable on CT scans.

With respect to tumours, RCR (2007) state that CT is sufficient to detect supratentorial lesions and can be helpful, in the acute setting, to exclude a bleed or mass in the posterior fossa, despite its difficulties in imaging this area.
Conclusion
The role of imaging of the unconscious patient in the acute phase should be to establish any underlying causes and best direct therapy. The therapeutic window for many of the differentials is narrow and so speed, accessibility and suitability (with regards to safety) need to be taken into consideration. It seems clear that MRI, in most cases, offers superior image quality and a higher sensitivity to many pathologies (particularly in stroke and posterior fossa pathologies), but in the acute situation, the risks to a patient who cannot be appropriately safety checked would not outweigh the benefits of the scan. It is most likely in this case therefore, that CT would be the first line investigation, with a potential to further investigate with MRI if necessary, once safety has been established.
2) A 25-year-old female gym instructor in the first trimester of pregnancy with acute knee pain and restriction of movement, following a circuit training injury. Plain X-rays show no apparent fracture.

Differential Diagnoses
In the presence of normal radiographs, one has to consider whether there are soft tissue injuries present in this patient. This could include injury to ligaments, tendons or menisci, all of which can have serious long-term implications for the patient (Dandy & Edwards, 2004).
Meniscal tears seem the most likely injury in this case as they are very common, can be caused by seemingly minor trauma, and patients often present with knee ‘locking’ due to loose meniscal fragments in the joint (Dandy & Edwards, 2004). Anterior cruciate ligament (ACL) injuries are also very common and can be associated with other injuries such as meniscal tears and bone bruising (Dandy & Edwards, 2004; Tham, Tsou & Chee, 2008). Posterior cruciate ligament (PCL), and collateral ligaments injuries are much less common (Colvin & Meislin, 2009; Dandy & Edwards, 2004).
A thorough physical exam must be performed to establish whether the patient is likely to require further imaging. There are various physical tests to determine knee instability that can be found debated in the literature (Colvin & Meislin, 2009). In fact, some studies have argued that clinical examination has a better sensitivity, specificity and accuracy than MRI in diagnosing medial meniscal tears, and was only as accurate at diagnosing lateral meniscal and anterior cruciate ligaments (Rayan, Bhonsle, & Shukla, 2009).
Diagnostic Value of MRI
MRI offers excellent tissue contrast and high spatial resolution, can be performed in any plane and is good at demonstrating meniscal and ligamentous anatomy and integrity (Armstrong et al., 2009). The main value of performing an MRI is to reduce the number of patients referred for arthroscopy, which is an invasive procedure (Crawford, Walley, Bridgman & Maffulli, 2007; Aiello, 2010). Armstrong et al. (2009) state that some surgeons will only use MRI in patients for whom the diagnosis is not clear, and will often progress straight to arthroscopy, when internal derangement of the knee is clinically suspected. RCR guidelines (2007) state that MRI is warranted in suspected injuries of ligaments and menisci. MRI can also show other pathologies that may not be diagnosed on arthroscopy such as bone bruising and adjacent pathology that is not contained within the joint capsule.
SNR can be maximized in all sequences by the use of dedicated extremity coils, allowing for very high resolution (Westbrook et al., 2005; McRobbie et al., 2003). Sequences used vary between clinical sites, but a combination of T1, T2 and protein density (PD) sequences are commonly used to best demonstrate anatomy and pathology (McRobbie et al., 2003; Tsou, Yegappan, Ong, & Goh, 2006). STIR or fat-suppressed T2-weighted images can show oedema in muscles, tendons or bone (Bencardino, et al., 2000). The use of dedicated three-dimensional (3D) knee sequences, such as 3D-SPGR (spoiled gradient echo) or DESS (Dual echo in the steady state) can maximize SNR and allow good resolution down to 1mm (Tsou et al., 2006). Fast spin echo (FSE) can be helpful in injuries as they are less prone to susceptibility artefacts from blood products (Tsou et al., 2006), but others have argued that FSE with long echo train lengths can cause blurring on the images (Aiello, 2010).
Menisci
Armstrong et al. (2009) state that the menisci are well demonstrated on MRI due to their different signal intensity from the articular hyaline cartilage. They have low signal on all sequences as they are fibrocartilagenous, and will appear as a bow-tie construction on sagittal images. Meniscal tears (figure 6) disrupt the articular surface and are best demonstrated as high signal on PD-weighted images with a very short echo time, typically less than 26ms (Aiello, 2010). However, if too low echo times are used, high signal can be seen in normal meniscus due to the magical angle phenomenon (Aiello, 2010). False positives have been reported, due to variable anatomy or chondral injuries mimicking tears of the menisci (Nicolaou, Chronopoulos, Savvidou & Plessas, 2008). Aiello (2010) states though, that if a meniscal tear is seen on two consecutive slices, then the accuracy approaches 100%. Crawford et al. (2007) found that MRI was good at demonstrating medial meniscal injuries (sensitivity 91.4%), but was poorer at diagnosing lateral meniscal tears. Conversely, MRI can occasionally show meniscal tears that are not demonstrated on arthroscopy (Armstrong et al., 2009).

Ligaments
Crawford et al. (2007) describes the ACL as a low signal structure located in the intercondylar notch (Figure 7). Partial tears may be seen as a high signal on T2-weighted imaging (Crawford et al., 2007). Tham, Tsou & Chee (2008) report a sensitivity of up to 96%, and specificity up to 98% for diagnoses of ACL injuries in MRI (Figure 8) when compared to the gold standard of arthroscopy. In imaging the PCL, Colvin and Meislin (2009) report a sensitivity and specificity of almost 100% for MRI demonstrating complete tears.

Safety Concerns
This patient is in her first trimester of pregnancy and so careful consideration needs to be taken when considering whether MRI is the best imaging modality to investigate her knee injury. Reports from both the National radiation protection board (NRPB, 1991 sited in MHRA, 2007a) and the International Commission on Non-ionizing Radiation Protection (ICNIRP, 2004) have stated that there is no clear evidence linking either static magnetic fields, or time-varying magnetic gradient fields to adverse effects in pregnancy. However, the effect of radiofrequencies (RF) on tissue heating raise concerns as the developing foetus is regarded as being more sensitive to increased temperatures, this being particularly pertinent during organogenesis (De Wilde, Rivers & Price, 2005). It is difficult to measure the amount of heating a foetus is exposed to during scanning, as specific absorption rates (SAR) limits set by manufacturers are calculated according to an optimal ambient temperature of the room- and can subsequently be very inaccurate (De Wilde et al., 2005). The ICNIRP (2004) therefore recommend that exposure to RF during pregnancy is kept as low as reasonably possible. There are also concerns raised regarding the exposure of the foetus to acoustic noise, however there don’t appear to be any long-term studies to substantiate this (International Electrotechnical Commission, 2002 sited in MHRA, 2007a; De Wilde et al., 2005).
The ICNIRP (2004) conclude that pregnant patients, particularly those in the first trimester, be excluded from MRI except in cases where a critical analysis of the risk/benefit ratio has been undertaken, and it is deemed necessary to use MRI to investigate an important clinical maternal problem, or to manage complications in the pregnancy. The position of the Medicines and Healthcare products Regulatory Agency is that the decision to scan a pregnant patient should be made in consultation with the patient, the referring clinician and the MR radiologist, and that this discussion should be recorded in the patients notes (MHRA, 2007a).
One can hypothesize that in this case, there is little RF exposure to the foetus as the knee extremity coil would be transmit/receive and localized to the knee. However, there would still be exposure of the foetus to the fringe fields, time-varying magnetic fields and acoustic noise, albeit to a lesser extent, as the foetus is likely to be external to the magnet bore.
Alternatives to MRI
Arthroscopy is considered the gold standard for examining the menisci and cruciate ligaments and most studies highlighting the efficacy of MRI in examining the knee compare the results to the findings on arthroscopy (Crawford et al., 2007; Tham, Tsou & Chee, 2008; Rayan, Bhonsle, & Shukla, 2009). However, the accuracy of arthroscopy is dependent on the experience of the surgeon, and there are some areas of the joint that cannot easily be examined. Overall, the accuracy of arthroscopy is reported to be 70-100% (Nikolaou et al., 2009).
Arthroscopy is known to have surgical risks such as infection, vascular injuries, nerve damage and pulmonary embolism, but these are mainly associated with corrective surgery. MRI is less invasive, quicker and considered to be a useful screening tool alongside careful physical examination prior to patients being referred for arthroscopy (Crawford et al., 2007).
Ultrasound examinations can be performed but a study by Azzoni and Cabitza (2002) found that it was not sufficiently accurate to diagnose meniscal tears (sensitivity 60%, specificity 21%). Ultrasound appears to be better at detecting ACL injuries with a reported sensitivity of 88% and specificity of 98%, however this involved a small number of participants (n=62) (Larsan & Rasmussen, 2000). With regard to imaging the PCL, Miller (2002) found it reliable to show PCL rupture, and advocated that it could be a useful adjunct in patients for whom MRI was not an option.
Conclusion
This is a difficult case. This is a young patient with a physically demanding job. Leaving the injury untreated may lead to long-term problems and decreased quality of life. MRI has been proven to be a reliable screening tool in the diagnosis of many causes of knee pain, and has reduced the overall number of people being referred for invasive arthroscopy (Crawford et al., 2007). Although it uses no ionizing radiation, and there is no convincing evidence that it may be harmful to the developing foetus, it is not recommended in first trimester of pregnancy (MHRA, 2007a). In deciding whether the patient should have the MRI, a thorough examination by an experienced orthopaedic surgeon should be performed (Dandy & Edwards, 2003). Ultrasound may be helpful, but due to its poor depiction of meniscal injuries, a negative ultrasound will not rule out a knee injury. An arthroscopy is considered the gold standard test, and the patient may be referred for one if clinical suspicion is high, with or without a positive MRI scan. Arthroscopy has its risks also. The clinician must help the patient make an informed choice weighing up the risk-benefit- ratio.
Final word count approximately 3111 (excluding all references and citations)
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