Brain Imaging, Crash Course

Welcome back everyone This is Dr. Rybinnik Imaging is part of our daily professional life in neurology So, let’s give you a crash course in reading it This video is rated “MS” for medical students due to basic concepts, clear language and case-based examples Medical student participation is advised Our objectives for this talk are to: Introduce a case that will act as the glue keeping the sections together Introduce an approach to reading imaging Review major anatomical landmarks so you can find your way around scans Assess the degree of symmetry (or asymmetry), to allow you to spot abnormalities Review the causes of hyperdensity and hypodensity on CT Since we are on the topic of hypodensity, we will introduce the concept of cytotoxic and vasogenic edema Edema will transition nicely into a discussion of the causes of hyper- and hypointensity on various MRI sequences We will conclude with a review of patterns and locations of enhancement, and summarize Let’s start with a case It just got real You are asked to see the following patient This is 73-year-old previously healthy woman With weeks of memory difficulties, 10 days of increasing lethargy, 3 days of urinary incontinence, and now mild left sided weakness and rigidity Head CT was already conveniently done for you by the emergency department team Radiology resident has passed out Your neurology resident is running a stroke code It is up to you to diagnose this patient First things first, it’s the clinical history and not imaging that will lead you to the final diagnosis Imaging can at best help you with a reasonable differential So, whenever facing the unknown it’s useful to have an approach First step is to identify the scan, the imaging sequence, and the slice Then look for symmetry, or more appropriately, asymmetry Next, we need to identify the lesion causing the asymmetry, and its density/intensity, decide if contrast enhancement pattern may be useful, and locate the lesion in the extra-axial compartments (outside the brain), or intra-axial compartment (in the brain parenchyma) Put all this data in a blender, puree it, and you get the delicious smoothie that is the final differential diagnosis First up, landmark review And for our landmarks, we’ll use the head CT Head CT without contrast is the most common imaging modality that we get Contrast can be added to look for breakdown of blood brain barrier, for example with neoplastic or infectious lesions, but that’s better seen on MRI CT can be used to obtain vascular imaging by rapidly tracking a bolus of contrast into the brain This is called a CT angiogram The difference between CT with contrast and a CT Angiogram is essentially the timing of the scan with respect to the contrast injection CT angiograms are really powered to identify vessels, not brain parenchyma And finally, CT-based perfusion can be used to estimate brain blood flow But, for the purpose of this talk, the only sequence we will focus on is the plain old non-contrast head CT Here is a typical normal head CT, axial slice with a cut through the orbits You can even make out the lenses inside the eyeballs By convention, the patient is lying in front of you on a table, feet first like in the anatomy lab or the operating room So, the nose is pointing up Patient’s left is on your right, and the back of the head is on the bottom of the slide In this image, we are looking a bit higher in the brain This slice is taken though the upper frontal and parietal lobes How do I know that? Well, the slide is labeled A better method is to locate the central sulcus It makes a curve that looks like the Greek letter “omega.” Anything anterior to that sulcus is the frontal lobe, and posterior is the parietal lobe Fun fact, the “omega” looking bump in the pre-central gyrus is also called the “hand knob.” This is where the motor control of the hand resides Since we on the topic of anatomical localization, we should probably quickly introduce the T1 sequence of the MRI T1 is the called the “anatomical” sequence because it shows white matter as white, and grey matter as grey as they would look on gross pathology Can you still identify the “omega sign?”

Yep. Here it is on the scan And if you need extra help, Netter’s to the rescue Scanning lower down, now we are at the level of the basal ganglia Lateral ventricle is in the middle Head of caudate in next to the frontal horn of the lateral ventricle Thalami are separated by the 3rd ventricle Head of caudate and thalamus are separated from the lentiform nucleus by the internal capsule More laterally, you will find the insular cortex covered by the anterior temporal lobe Now, can you identify those structures on a T1 image? Head of caudate Thalamus Internal capsule Lentiform nucleus Insula And anterior temporal lobe Here is an illustration Moving right along This is a slice through the sylvian fissure Incidentally, the orbits and eyeballs are back What lives in the Sylvian fissure? Yes, the middle cerebral artery Here it is, isodense to the brain parenchyma It’s generally very difficult to distinguish from the nearby brain But, when you can make it out because it is brighter, that’s when you know things are bad More on that later Here is the sylvian fissure on T1 As you can see on the localizing image in the upper left corner, T1 and CT slices are not necessarily at the same angle So, on this T1 you can actually make out the mickey mouse-looking midbrain And once again, the Netter illustration Speaking of the midbrain, here is the CT axial cut at the level of the midbrain The midbrain is central here with the CSF-filled basal cistern right behind it The medial temporal lobe or uncus is lateral to the midbrain Uncus, as in uncal herniation The uncus may herniate onto the midbrain, so needless to say it’s important to be able to locate it More on that in the coma talk Next, temporal horn of the lateral ventricle Normally, as in this example, it’s slit-like If it becomes dilated, this is one of the earlier signs of hydrocephalus Moving lower down, now we are at the mid-pontine level Here is the pons with its brachis pontis – “arms of the pons” or cerebellar peduncles It’s as if the pons is reaching out to the cerebellum for a hug While the pons and the cerebellum are hugging, the structure in the middle of the hug that feeling the love is the 4th ventricle The place where brachis pontis meets the cerebellum is called the… wait for it… cerebello-pontine angle Later in the talk, we’ll take a look at some mass lesions in this area Here is what the pons looks like on T1 Where is the 4th ventricle? Getting hugged. Right in the middle And here is the illustration Now this slice is even more caudal (or lower) Here is the medulla with the 4th ventricle adjacent to the cerebellum Look at how much better the resolution of MR is, especially in the posterior fossa Here is the illustration of the same thing And finally, the foramen magnum with the cervical spinal cord bathed in CSF So, now that you are an expert, let’s make things a little more challenging Can you identify the major landmarks on our patient’s head CT? Pause the video now First, let’s identify the ventricles: Frontal horn of the lateral ventricle, occipital horn of the lateral ventricle, and the third ventricle Now, you should be able to locate the basal ganglia structures: Caudate head, thalamus separated from the lentiform nucleus by the internal capsule, then more laterally, the insula covered by the anterior temporal lobe Well done, grasshopper! Progress to the next level Let’s talk about symmetry Here is a non-contrast head CT, axial slice through the basal ganglia This image should haunt you in your nightmares by now Let’s locate the midline by drawing a line from the falx cerebri to the confluence of venous sinuses, right through the septum pellucidum in the middle of the lateral ventricle There is no asymmetry here, and midline is where it needs to be Now, what about this slice through the pons?

Also symmetric By the way, whenever you see overlapping slices during this talk, both slices come from the same study and the same patient What about in this picture? Is there asymmetry? Absolutely Once you spot asymmetry, look for a lesion causing it It has to be on the patient’s right side, since the shift is towards the left And here it is – a concave subacute subdural hematoma What about in this image? Again, there is significant mass effect and midline shift But this time, the lesion is a massive acute right middle cerebral artery stroke Don’t worry about how I figured out what these lesions are That’s for the next section Who’s up for another challenge? Let’s analyze a posterior fossa slice Who says there is a lesion on the patient’s right? The patient’s left? No lesion? Let me highlight the pons, the 4th ventricle, and the cerebellum Does that help? Yes, there is definitely midline shift Now, what’s causing the mass effect? There is a mass at the cerebellopontine angle You see how difficult it is to pick up on CT? This happens to be a vestibular schwannoma And finally, not all asymmetry is just about midline shift Does this image look symmetric to you? No There are two subcortical hypodensities that are present on the patient’s the right side, but not on the left This happens to be a patient with toxoplasmosis Again, don’t worry about how I knew that All shall be revealed in it’s own good time Let’s return to our case once again Is our patient’s scan symmetric or asymmetric? Asymmetric Now look for a lesion causing the asymmetry Here it is Now that you have an understanding of the basic approach to a head CT, it’s time to talk about density [Star Wars “The Force” theme plays] Step into the light, young Padawan Hyperdensities on the CT are easy to spot, and by design, which makes them an excellent diagnostic tool Bright signal on CT is caused by mineralized structures, such as calcium-rich bone and chronic calcified lesions But also head CT is wonderful at detecting acute blood, with a sensitivity of above 90% Before we get bloody, I want to remind you that not all hyperdensities are abnormal Here is a non-contrast head CT axial cut through the sylvian fissure Calcified pineal, calcified choroid plexus, and bone are some examples of normal hyperdensities What about this image? There are multiple calcified lesions in the left hemisphere, and a small one in the right thalamus I’m about to ruin your appetite This is calcified scolex of the tapework taenia solium You probably know this disease by another name – neurocysticercosis It’s a common cause of seizures worldwide On this image, the lesion is less dense, and less bright than calcium and bone This basal ganglia hyperdensity is an acute hemorrhage, with some intraventricular extension There is the hyperdensity on this scan? It looks like all the sulci were outlined by chalk There is diffuse hyperdensity in the subarachnoid space, which is extra-axial (outside the brain parenchyma) It’s a great example of diffuse subarachnoid hemorrhage, with some intraventricular extension of blood Once again, identify the midline shift then look for a lesion causing it There is an extra-axial lens-shaped hyperdensity respecting suture lines You can actually adjust the contrast setting on the CT to “bone window.” This will help you identify body abnormalities like fractures, and landmarks, like sutures At this point, it’s probably painfully obvious that this is an example of epidural hemorrhage If the last image was an example of an Epidural, this is a subdural hemorrhage

Identify midline shift, look for a lesion causing the shift, and identify the lesion location We know this lesion is located in the subdural space, because it is concave and crossing suture lines and therefore extra-axial So, this game should be getting boring by now Time for another challenge Pause the video and identify abnormal hyperdensities on these two scans from two different patients The image on the left shows a serpentine hyperdensity outside of the brain in the sylvian fissure What lives in the sylvian fissure? That’s right, middle cerebral artery The image on the right also shows a hyperdensity But this time it’s between the cerebral peduncles (in the interpeduncular cistern) This is the top of the basilar artery You know that all acutely clotted blood looks hyperdense or bright on CT So, these dense vessel signs represent acute clots – pretty important information to have when treating a patient with suspected acute ischemic stroke [Dr. Rybinnik as Darth Vader] “Now come to the dark side and learn to use the dark side of the force.” [Normal voice] The dark side is more challenging to grasp, but holds great power for those who can wield it Fluid is less dense and appears dark on CT, so hypodensities usually reflect chronic lesions, cysts, or cerebral edema Let’s look at some examples First up, chronic damage This hypodensity is very well defined, wedge-shaped, same density as the CSF, and conforms to a vascular territory The brain on the right side looks shrunken, and the frontal horn of the right lateral ventricle is expanded as a result The proper name for this loss of brain tissue is encephalomalacia So, you probably guessed by now that this is an example of a chronic right MCA stroke Where is the encephalomalacia on this image? You’re right It’s bifrontal More so on the left but the right is abnormal too This does not conform to a vascular distribution Bilateral frontal lobes are a common site of trauma, and this is an example of chronic traumatic brain injury How is this hypodensity different? Is it involving the brain parenchyma? Is this encephalomalacia? It looks well-defined, but also smooth unlike the previous examples The location of this lesion is extra-axial with similar density to CSF because it is a CSF-filled structure This is an example of a fronto-temporal arachnoid cyst, which is fairly benign but may become large enough to exert mass effect and cause seizures Get ready for your next challenge Is there a hypodensity and if so, which side? [Dr. Rybinnik as Darth Vader] Feel the dark side of the force calling to you Difficult isn’t it? There is a large faintly hypodense lesion within the right MCA territory You may remember that acutely ischemic neurons swell, but that edema takes several hours to show up on the head CT Let’s just say 6-8 hours on average So, it’s very challenging to detect edema related to acute ischemic stroke on the head CT in the first 6 hours In fact, most early head CTs in acute stroke patients are normal This scan was done 8 hours after symptom onset Here is another example What’s unique about the abnormality on this scan? Hopefully you noticed the finger-like subcortical hypodensities Looks like a giant hand gripping a small ball Well, that ball is a brain metastasis, and the hypodense “hand” is another type of cerebral edema You can see how the hypodensity on the CT can only take us so far Time to introduce the MRI [Sherlock Holmes] “Data! Data! Data! Icannot make bricks without clay,” [Normal voice] as the famous fictional detective Sherlock Holmes would say

It’s worth noting that when placing a standard order for a non-contrast MRI of the brain, you typically get the following 4-course meal T1 weighted imaging for appetizer Your main course will be T2 weighted imaging with a side of T2 derivative called Fluid-Attenuated Inversion Recovery (or FLAIR), arguably the most filling and useful sequences The cheese and fruit plate would be Diffusion Weighted Imaging and its evil twin, the Apparent Diffusion Coefficient, which are essentially designed to diagnose energy failure/ischemia And for dessert, we have the Gradient Recalled Echo sequence (or GRE) to detect hemorrhage If you want to finish your meal with a cup of delicious coffee, may I suggest T1 with Gadolinium contrast? But this must be ordered separately, and you have to pay extra MRI can also image vasculature, which requires an order for an MR angiogram Finally, there are numerous specialized sequences including fat suppression, perfusion, spectroscopy, tractography, etc There are more fancy MRI sequences than Ben and Jerry Ice Cream flavors MR angiogram and special sequences are outside of the score of this talk You can’t digest everything in one meal So, take a normal head CT Zoom in And adjust contrast You can plainly make out two different tissue densities The lighter, or less dense is the grey matter And the darker is the subcortical white matter The junction where the two meet is called… wait for it… the grey white junction Now let’s bring in the T2 Fluid is bright on T2, so identifying fluid filled cell bodies of the cortical grey matter and distinguishing them from the darker subcortical white matter, and the subcortical gray matter is much easier What is actually happening on a cellular level in all crevices? I know, I know, you are probably allergic to basic science. But stay with me Have you heard of the neurovascular unit? This unit consists of astrocyte foot processes wrapped around capillary endothelial cells, which are connected by tight junctions Brain parenchyma filled with neurons is outside, and blood is inside the capillary lumen You may call it a barrier between blood and brain Oh! Neurovascular unit is the essential component of the blood brain barrier, and blood brain barrier surrounds the entirety of brain parenchyma What happens when the neurovascular unit is deprived of blood flow? Astrocytes, capillary endothelial cells and neurons become ischemic They can’t maintain the sodium potassium gradient, and take on fluid Despite that, the blood brain barrier remains essentially intact early on This is called cyto-toxic (or cell body) edema, because it’s toxic to the cells Here is a patient with acute right middle cerebral artery stroke Edema is everywhere – grey matter, white matter The cortical ribbon is completely lost, and the loss of this grey white junction is a clue that we are dealing with cytotoxic edema of ischemia T2 weighted imaging sequence is much better at highlighting that fluid Get it “highlighting!” Cause it’s bright? No. Allright The edema is bright, but CSF is also bright So, interpretation of this image is somewhat hampered by the CSF-filled sulci Here is an idea What if we subtract the CSF signal? Introducing – FLAIR Fluid-Attenuated Inversion Recovery sequence It’s unmistakably related to T2, since grey matter is lighter than white matter and fluid appears bright, with one important exception The bright signal from CSF has been subtracted, and now you can quickly identify the abnormality from across the room Now, imagine that instead of energy failure, the integrity of the neurovascular unit is compromised The tight junctions become leaky, allowing the plasma to escape into the interstitial space This type of edema is called vaso-genic, as in poor vessel integrity This happens with neoplasms and cerebral abscesses, which secrete substances that increase blood brain permeability, brain trauma, which can cause mechanical disruption, and even very high blood pressure that can overwhelm the neurovascular unit’s ability to regulate fluid flow across the capillary endothelium In this example,

a brain metastasis caused these finger-like projections of vasogenic edema, which is much better seen on the T2 weighted imaging The edema essentially stops at the grey-white junction and does not affect the grey matter The cortical ribbon is preserved, and you can make out the angry heterogeneous mass in the middle And of course, you can see the full extent of the edema better on FLAIR So, one more time: Vaso-genic edema because of failing neurovascular unit integrity (which can be caused by tumors, abscesses, trauma and severe hypertension), and cyto-toxic edema or cell-body edema caused by energy failure and ischemia Got it? Look at the hypodensities on CT – how much more inferior they are to the FLAIR and T2 T2 and FLAIR are superior by design And just when you thought the dark side was winning the light strikes back With CT, it’s all about density With MRI, it’s all about intensity Bright signal is easiest to see, so we’ve been tackling edema first If MRI were a book, the first chapter would be called “Look on the bright side. It’s swollen.” So, we discussed non-contrast head CT, T1, T2 and FLAIR When it comes to cytotoxic edema caused by ischemia, T2 and FLAIR kind of behave like CT It takes hours for a lesion to build up enough cerebral edema to show a bright signal Diffusion Weighted Imaging is designed to detect ischemia earlier – within the first 30 minutes from onset Apparent Diffusion Coefficient is DWI’s evil twin It’s the anti-DWI Ischemia will cause bright signal on DWI, and dark signal on ADC Well, all of this seems overly complicated You’re telling me, that we need another sequence of the MRI to be confirmed with yet another sequence of the MRI? Unfortunately, yes And here is why DWI is related to T2 and FLAIR So whatever is bright on DWI, will also be bright on those sequences Or it’s probably more accurate to say that whatever is bright on T2 and FLAIR will also be bright on DWI This phenomenon is called T2 shine through T2/FLAIR abnormalities shine through to the DWI Now, look at the ADC Is this an example of an acute stroke? No! ADC is bright not dark, like in the last example This is T2 shine through Bottom line always check DWI against ADC to confirm acute ischemia Our brightness motif continues Here is another T2/FLAIR pair of sequences from the same study What kind of edema is this? Vasogenic or cytotoxic Finger-like projections, gray matter unaffected Has to be vasogenic This is an example of a brain abscess in the right parietal lobe Incidentally, abscess-forming organisms usually spread through the bloodstream from a primary site, and of course more of these emboli will end up in the vascular territory of the artery that supplies the majority of the hemisphere So, it’s not surprising that the most common locations of abscesses are in the frontal and parietal lobes in the distribution of the middle cerebral artery Again, we are really focusing on the bright signal here From these sequences alone, you cannot unequivocally distinguish an abscess from another mass You need other sequences of MRI, but more on that later Speaking of masses, what is the most common neoplasm in the brain? That’s right. Metastasis! What is the type of edema pictured on this T2 image? Right again These are finger-like projections of vasogenic edema, and you can make out the small, well-defined, round masses that are isointense to the brain parenchyma Let’s bring back our illustration of the cortical ribbon Have you noticed that these metastatic lesions are near the gray-white junction? Nearly 80% of mets are That is because like bacteria, metastasis generally spread through the bloodstream, and arterioles at the grey-white junction are just small enough to trap traveling neoplastic cells Lung and breast cancer metastases are the most common This example happens to be lung cancer, but again the imaging is never that specific Tissue biopsy is generally necessary to confirm the tumor type Say, one of those metastases moves into the posterior fossa,

exerting tremendous mass effect on the 4th ventricle What is the abnormality on this FLAIR sequence? Notice the symmetric smooth hyperintensity that is periventricular Under pressure, CSF is being pushed out of the ventricle across its walls (or ependyma) into the brain parenchyma So, this transependymal flow of CSF is seen in obstructive hydrocephalus Lateral ventricles are also certainly dilated In this case, the hydrocephalus was caused by a posterior fossa mass obstructing the 4th ventricle below the level of this slice Let’s move on to the next example of FLAIR hyperintensity This is a sagittal image just lateral of midline, with the patient looking to your left How would you describe the abnormalities? You probably said that these are ovoid periventricular hyperintense lesions These are “Dawson’s fingers” in a patient with multiple sclerosis And, on the axial FLAIR image, you can see them as well Ovoid lesions That’s a strangely specific appearance Do you know what that happens? Well, there are so-called central veins running perpendicular to the ventricles (This is one of those fancy MRI sequences that we won’t cover in this talk.) In MS, immune cells exit these veins and penetrate the brain parenchyma here, causing this ovoid-appearing inflammation How is this image different? Is this another example of a patient with multiple sclerosis? The hyperintensities are still periventricular and subcortical, but they are more confluent not ovoid Also, the sulci are quite deep and prominent because of significant brain atrophy Confluent subcortical lesions with brain atrophy in a patient with vascular risk factors are likely caused by small vessel ischemic disease Judging by how ugly this image looks, you would probably expect this patient to have vascular dementia Small vessel ischemic changes are so common, that I’m showing them to you twice Now that we discussed bright signals on T2 and FLAIR, let’s quickly mention bright signals on T1 Generally, bright signal on T1 is caused by: Paramagnetic substances (like iron, copper, melanin, calcium), fat, protein-rich lesions, and subacute bleed Here is an example of metastatic melanoma in the right eyeball It is showing up as a T1 hyperintensity Note that the orbital fat is also bright on T1 That’s normal How about this example? The bright signal in the basal ganglia corresponds to pathological copper accumulation This is Wilson’s Disease – an autosomal recessive disorder where a gene mutations cause impaired trafficking of copper in and through the hepatocytes, so it deposits in many organs and tissues, including the brain And more last example This well-circumscribed T1 hyperintensity corresponds to a mass at the foramen of Monro which is protein-rich This mass is called a colloid cyst It’s claim to infamy is that it can act like a ball-valve, occluding the Foramen of Monro and causing hydrocephalus This can happen so acutely and so severely, that it can kill Blood in the brain doesn’t quite play by the rules, and its intensity on T1 and T2 actually evolves over time In the first several days, the hematoma containing deoxy hemoglobin looks isointense on T1 and darkens on T2 Beyond 3 days from bleed onset, both T1 and T2 signals brighten as deoxy hemoglobin is converted to met hemoglobin Ultimately, the site of hemorrhage is essentially replaced by a CSF filled slit-like hole, which looks dark on T1 and bright on T2, as fluid does It sort of looks as if the brain has been stabbed, and there is usually hypointense signal on T2 representing the rim of hemosiderin, which is like a fingerprint left by the chronic hemorrhage What is the stage of this hematoma? Right, it’s late subacute stage (about 3-14 days) Both T1 and T2 are bright [Signs] Whew! That was a long section, but it had to be

MRI is really designed to highlight lesions, so most abnormalities will be hyperintense A brief summary: T2 and FLAIR brightness will help you diagnose: Ischemic stroke (DWI is also indispensable for stroke), vasogenic edema (due to metastatic disease, brain abscess), transependymal CSF flow due to hydrocephalus, inflammatory lesions like the ovoid lesions of multiple sclerosis, small vessel ischemic changes, and subacute hematoma T1 brightness will help you diagnose: Metal deposition like copper in Wilson’s disease, other paramagnetic substances like melanin in this ocular melanoma, fatty lesions, which we didn’t really cover, protein-rich substances, like a colloid cyst, and subacute hematoma I for one dislike mnemonics because eventually all I remember is the words not what they stand for But if you need one, here it is: “Shine and shimmer.” S2HI2NE for T2, and SHIMMeR for T1 S2HI2NE: Stroke and subacute hematoma, hydrocephalus, ischemic and inflammatory lesions, neoplasms, and edema SHIMMeR stands for subacute hematoma, iron, metals, melanoma, and “rich in protein.” Now let’s switch gears and talk about hypointense lesions Lesions or structures that appear dark on T2 are essentially the same ones that appear bright on T1 Well that was easy We are once again talking about: Protein-rich masses, paramagnetic substances like iron, copper, melanin, and calcium Flowing blood inside of blood vessels does not get imaged on T2 and also appears dark And hematomas make their own rules, so acute hematoma looks dark on T2 Hey no, get out of here, Kylo Ren! The light side of the force rules MRI That protein-rich colloid cyst we just saw that as bright on T1 appears dark on T2 Flowing blood is not imaged, so it creates dark signals called flow voids on T2 These are two T2 slices from the same study Pause the video now and identify all the flow voids on these images Time for a circle of Willis review Internal carotids, MCAs, PComms, and PCAs But there is just one more – the confluence of venous sinuses What’s wrong with this T2 image? Maybe an illustration will help There is a flow void corresponding to the ICA on the patient’s left Where is the flow void on the right? Absent The right carotid is occluded I’m giving you this next example because this radiological sign has a really cool name This is disease is called Pantothenate Kinase-Associated Neurodegeneration (pantothenate is Vitamin B5) Please don’t memorize it, it’s rare Essentially, it’s an autosomal recessive disorder where a mutation disrupts energy and lipid metabolism and can lead to accumulation of iron or copper in the brain Remember Wilson’s disease? Was that lesion bright or dark on T1? Bright And T2 is opposite of T1, so the dark signal on this T2 in this image is iron accumulation The bright signal is gliosis, which corresponds to the iron-damaged basal ganglia This sign is called the “eye of the tiger.” And finally, acute hematoma On this T2 image, this basal ganglion hematoma appears dark surrounded by a small rim of edema Is this vasogenic or cytotoxic edema? I’ll leave that to you to look-up We talked all about dark signals on T2, but T1 is generally only useful as a baseline against which to compare hyperintensities on T2 and other sequences Hypointensities on T1 are chronic lesions and fluid, and chronic lesions are filled with fluid, so it makes perfect sense T1 in this respect behaves a bit like a CT For example, you can use T1 to see chronic lesions in multiple sclerosis These are known as “black holes.” Incidentally the number of black holes correlate with disability Quick recap T2 hyperintensities are caused by: Protein-rich lesions like the colloid cyst, flow voids corresponding to normal circle of Willis vessels and venous sinuses,

deposition of paramagnetic substances like iron in this example, and acute hematoma When it comes to hypointensity on T1, it behaves like the non-contrast head CT showing fluid-filled lesions as dark And if you need a mnemonic, how about “fab pic” (fabulous picture) Flowing or acute blood, protein, iron and other paramagnetic substances, and chronic lesions on T1 One more time. Let’s do it together! What is hyperintense on T2? Cytotoxic edema of stroke, vasogenic edema of tumors and abscesses, transependymal flow of hydrocephalus, subacute bleed, and inflammatory lesions of disorders like MS Fluid that is bright on T2 appears dark on T1 So edema and chronic lesions are hypointense What is hypointense on T2? Paramagnetic substances, protein-rich lesions, flowing blood, and acute bleed What is hyperintense on T1? Paramagnetic substances, protein-rich lesions, fat, and subacute bleed [Skywalker] “Master, moving stones around is one thing This is totally different.” [Yoda] No! No different! Only different in your mind” “You must unlearn what you have learned.” [Skywalker] “Allright, I’ll give it a try.” [Yoda] “No!” “Try not.” “Do! Or do not.” “There is no try.” Now let’s get back to our patient Brief reminder, the non-contrast head CT showed a large confluent white matter hypodensity and a small hyperdensity Let’s proceed with T1 What is dark on T1? Edema So T1 did not provide any more useful information than CT, so we generally skip it Next up, T2 and FLAIR You can obviously see the huge hyperintensity on T2, and even more so on FLAIR Considering that we spent a huge chunk of the talk identifying edema, which edema is this? These are finger-like projections of subcortical vasogenic edema, which spares the cortex Do you see any other abnormalities? There is one more mystery left to solve – that little hypointensity in the frontal lobe I keep forgetting, what is usually dark on T2? Proteinaceous lesion, flow voids, paramagnetic substances like iron and acute blood Aha! So, this is a lesion with tremendous amount of vasogenic edema and small acute hemorrhagic focus But we are still missing one crucial piece of information to help us crack this case And without further ado, we enter the final stage of our journey together – the patterns and locations of enhancement [Dr. Rybinnik speaking with Yoda’s voice] “Return to the light, you must.” [Normal voice] Start with the normal T1 sequence Now add Gadolinium contrast Gadolinium is a ferromagnetic substance, that when injected intravenously shows up as bright signal on T1 So, you can see arteries, like MCA and PCA and veins like the left transverse venous sinus Also fat, which is also bright T1, has been subtracted on the contrast image to avoid confusing it with contrast You can barely make the orbits here, which are typically fat-filled Let’s bring in some other more rostral slices from the same study, and fill them with contrast Again, you can see the serpentine vessels traveling in the sulci, and deep draining vein and superior sagittal sinus Bottom line, seeing contrast outside of the brain in the sulci may be normal, but since Gadolinium does not cross the blood brain barrier, you should never see enhancement in the brain parenchyma or the meninges when the neurovascular units are intact So, let’s talk about what happens when the blood brain barrier is not intact Here are some common patterns of enhancement: Dural tail, leptomeningeal and periventricular are extra-axial, outside of the brain Ring, subcortical nodular, and mural nodule are intra axial, in the brain parenchyma There are certainly more types of enhancement than this, but this a solid sampling First up, the focal dural enhancement Here is an example of an enhancing dural mass How am I so confident stating that this is a dural mass? Well, two things First, there is a dark rim of CSF that separates the mass from the brain parenchyma This so-called CSF cleft tells us that the mass is extra-axial

And second, there is this dural tail This is a meningioma, most common extra-axial neoplasm Meningiomas are usually benign, but can grow large, cause vasogenic edema and invade venous sinuses By the way, dural tail mainly represents reactive changes to the meningioma and not necessarily neoplastic involvement Also, dural tail is definitely a distinguishing feature, but unfortunately it is not unique to meningiomas Dural mets can have dural tails too, but you will likely have other signs of metastatic disease, like weight loss, multiple lesions, etc Most meningiomas are supra tentorial, but how about this example? CSF cleft? Check Smooth homogeneously enhancing dural mass? Check Dural tail? Check This is another meningioma, but this time at the cerebellopontine angle Now what about this lesion? How is it different? CSF cleft is present, so it’s an extra-axial mass It’s located at the cerebellopontine angle, and causes mass effect on the pons and 4th ventricle Enhancement seems more heterogeneous than in the meningioma on the left There is a tail of sorts, but actually it’s more of a head than a tail, since the tumor extends from the internal acoustic canal This is an example of vestibular schwannoma, and that acoustic canal involvement is what helps us diagnose it Next, let’s talk about leptomeningeal enhancement Normal sulci are fluid-filled and appear dark on T1 So what’s abnormal? There is leptomeningeal enhancement all over And in a patient with fever and nuchal rigidity, you would be concerned about bacterial meningitis Well of course you are concerned! You ordered this MRI of the brain with and without contrast, right? Not all leptomeningeal enhancement is so obvious In fact most of it is quite subtle Can you spot areas of enhancement in these two slices from the same study? There is some serpentine leptomeningeal enhancement, but also enhancement around the pons and the medulla This is an example of basilar meningitis caused by tuberculosis Meningitis is the most common presentation of TB in CNS Since basilar meninges are involved, cranial nerves which are covered by those meninges are often dysfunctional as well (we are talking about cranial nerve VI, VII for example) And on more thing, CSF flow is often obstructed causing hydrocephalus This is yet another example of leptomeningeal invasion and enhancement, but this time by metastasis You have seen examples of solid mass metastasis at the grey white junction That’s the more common location Here, the tumor cells travel to the meninges Leptomeningeal carcinomatosis or carcinomatous meningitis is a rare complication of advanced cancer, usually breast or lung, just like any metastasis Notice the enhancement around the pons and in the cerebellar folia, especially on the sagittal slice I want to stress the fact how similar these three examples of leptomeningeal enhancement appear on imaging It’s not the imaging, but the history and CSF sampling that will help you differentiate between bacterial meningitis, tuberculous meningitis, and carcinomatous meningitis Since we are talking about metastasis, we might as well jump ahead and look at some examples of subcortical nodular enhancement You’ve seen this patient’s T2 imaging before when we discussed vasogenic edema Call out the lesions Multiple well-circumscribed enhancing mass lesions at the grey white junction surrounded by vasogenic edema, which appears dark on T1 With the appropriate history, this scan is the definition of metastatic disease What’s abnormal here? Once again subcortical, well-circumscribed enhancing nodule And on this slice And on this coronal slice with patient looking at you and patient’s left on your right So, what are these? Metastasis? Hmm. I don’t see any edema These look suspiciously ovoid and perpendicular These are acute multiple sclerosis lesions Next up, a medical student favorite – ring enhancement Ring enhancement generally implies a lesion with a necrotic center And your first example is a brain abscess Smooth ring-enhancing capsule Necrotic center Finger-like projections of subcortical vasogenic edema that is hypointense on T1 What about this lesion? Another abscess? You should know by now not to fall for that trick

It is a ring enhancing lesion, I give you that But the ring enhancement is irregular and there is involvement of the corpus callosum This is a high-grade invasive glioma, otherwise known as glioblastoma multiforme Now these are hand picked cases, but often the distinction is less obvious If only there were another MRI sequence to help… Enter DWI and its evil twin the ADC The lesion is bright on DWI and dark on ADC – true restriction of diffusion and not a T2 shine-through Remember that we talked about DWI in the setting of stroke and energy failure Brain abscess is another situation where DWI has high sensitivity and specificity Moving right along Multiple ring enhancing lesions with predilection for basal ganglia What if I told you that this patient has HIV? This is toxoplasmosis And you will often be asked to differentiate from another very similar lesion that occurs in this patient population – CNS lymphoma Can you spot the difference? There is a large solitary ring enhancing mass of lymphoma as opposed to numerous small ring-enhancing lesions of toxoplasmosis This lymphomatous lesion is in the basal ganglia in this case but doesn’t have to be, and in general it is more difficult to distinguish the two pathologies This is where another pattern of enhancement can help – periventricular enhancement Lymphoma has a predilection for periventricular region and subependymal spread (ependyma being the wall of the ventricle) Look at this neoplasm coating the ventricles Toxoplasmosis does not affect the ventricles This is lymphoma And the final enhancement pattern that we will discuss is the mural nodule, mainly because it’s so bizarre Imagine that this is a 14-year-old boy who slowly developed truncal ataxia to the left side, especially noticeable while playing sports His MRI with gadolinium showed this lesion It has a cystic component (fluid is hypointense on T1) and an enhancing mural nodule You can also seen that on the sagittal cut, with the patient looking to the left side of the slide This is an example of pilocytic astrocytoma, the most common infratentorial neoplasm in the pediatric age group, less than 20 years of age This astrocytoma is generally benign, but enhancement unfortunately suggests higher-grade tumor Remember the following enhancement patterns: Dural (menigioma and schwannoma), leptomeningeal (bacterial, tuberculous or carcinomatous meningitis), subcortical nodular (metastasis, acute MS lesions), ring enhancing (abscess including toxoplasmosis, and lymphoma), which affects the ventricles causing periventricular enhancement And mural nodule enhancement generally caused by pilocytic astrocytoma And if you need a mnemonic, try this one… MR lights the Damage Very Nicely “M” for mural nodule, “R” for ring, “L” for leptomeningeal, “D” for dural tail, “V” for peri-Ventricular, and “N” for nodular subcortical Now for the last time, let’s get back to our case Remember our lesion with tremendous amount of vasogenic edema and small acute hemorrhagic focus And this is the contrast enhanced T1 sequence What is the pattern of enhancement? This is ring enhancement, although it’s irregular and has some satellite lesions This lesion crosses corpus callosum At this point, the cat’s out of the bag This is a high-grade glioma I’m sorry to end on such a somber note, but I need this case to glue together multiple MRI sequences But on the bright side, we are done with this talk and we’ll move on to a really quick summary After obtaining clinical history, we typically start with a head CT Identify the slice and landmarks Basal ganglia is a good place to start Look for asymmetry, and the lesion causing asymmetry On CT, calcified structures and acute blood are bright, and chronic lesions, and edema or anything fluid-filled are dark Next, brain MRI without contrast Remember that you typically get T1, T2, FLAIR, DWI, ADC and GRE as a bundle when you order a non-contrast MRI An active lesion in the brain is usually identifiable by the edema it causes So, we should look at FLAIR first, since hyperintensity identifies edema Vasogenic edema is the result of failing neurovascular unit integrity,

which can be caused by tumors, abscesses, trauma, and severe hypertension Cytotoxic or cell-body edema is caused by energy failure and ischemia In general, bright signal on T2 may be caused by: Edema (stroke, tumors, abscess), hydrocephalus (due to transependymal flow of CSF), inflammatory pathology (such as multiple sclerosis lesion), and subacute hematoma (3-14 days from onset) Dark signal on T2 may be caused by: Paramagnetic substances (such as iron, copper, melanin), protein-rich lesions, flowing blood (flow-voids of normal circle of Willis vessels and venous sinuses), and acute bleed within 3 days from onset Next, if you are suspecting a pathology that will break the blood brain barrier like inflammation, infection, neoplasm order an MRI WITH and without contrast, and remember patterns of enhancement: Dural (like meningioma and Schwannoma), leptomeningeal (like bacterial, fungal and carcinomatous meningitis), periventricular (in the case of lymphoma), ring, (in the case of lesions with necrotic core like abscesses, toxoplasmosis, and lymphoma), subcortical nodular (like metastasis to the grey white junction or periventricular multiple sclerosis lesions), and mural nodule, such as in the case of pilocytic astrocytoma T1 without contrast is generally less useful for diagnosis with a few exceptions but can serve as a baseline template to which all other sequences can be compared Bright signal on T1 typically suggests: Paramagnetic substances (like iron, copper in Wilson’s disease, melanin in melanoma), protein-rich lesions like a colloid cyst, fat, and subacute bleeding 3-14 days from onset Dark signal on T1 basically corresponds to chronic lesions, which are filled with fluid DWI/ADC pair is extremely important for detection of early brain ischemia as well as brain abscesses True restriction of diffusion or energy failure is when a bright lesion on DWI looks dark on ADC In patients where we are concerned about stroke, we may even review this sequence first, right after the CT and before FLAIR Finally, remember that blood on MRI plays by its own rules Acute blood becomes dark on T2 within the first 3 days and slowly brightens on T1 Beyond 3 days, met hemoglobin creates a bright signal on T1 and T2 And that is all Thank you for joining us You should feel incredibly exhausted but hopefully wiser Go forth and read imaging studies Compare your impression with the radiologist’s report That’s how you learn Practice makes perfect! Until next time Bye [Beep] [Aladdin sings] “I can show you the world.” “Shining, shimmering, splendid.” “Tell me princess now when did you last let your heart decide.” “I can open your eyes…”