 Hello everyone, myself Dr. Mithusha Verma, I am a consultant radiologist reporting PET-CT, CTN MRI at the Department of Imaging Nanavatti Superspeciality Hospital, Mumbai. First of all, I would like to thank Indian radiologist for giving me this wonderful opportunity and an excellent platform. The topic which we are going to talk about today is 3D, RTG has been lately. In this topic, we divided into two parts. In the part one of the lecture series, we saw the basics and physics behind it. Also, we saw the application of ASL in stroke imaging. In this part, we are going to see ASL and its application in various other pathologies. Just to revise in brief, arterial spin labelling is a gadolinium-free MR perfusion technique which uses magnetically labelled arterial blood water protons as an endogenous tracer. Here, we obtain two sets of images. One are labelled or tagged images and the second set is of control image. By subtracting these two data sets, what we acquire is cerebral blood flow maps. ASL is an echoplane imaging technique and must be acquired before gadolinium administration since gadolinium will cause T1 shortening, leading to a decrease in the measurable signals. This is how a normal ASL colour map looks like. Usually, in standard techniques, what we use is rainbow colour spectrum format and whatever is towards the red part of the spectrum is relatively hyperperfused while whatever is towards blue part of the spectrum is relatively hyperperfused. Coming to the potential applications. There are several pathologies where actually we can use ASL to substantiate our diagnosis. Application of ASL in stroke we already saw how it helps us in determining the perfusion-diffusion mismatch in the setting of hyperacute stroke also how it helps us to differentiate stroke from stroke mimics. Coming to rest of the applications like in epilepsy imaging, dementia, tumor imaging, CNS infections and imaging, few of these psychiatric disorders. Starting with the role of ASL in epilepsy, as per whatever studies and literature review, as well as our practical experience, we know that ASL is useful to detect and characterize the epileptogenic focus. In other words, the CESA onset zone, SOC. In acute deficit, ASL can confer seizure diagnosis and help to rule out other mimics. ASL abnormalities are well correlated with EEG findings and ASL is more sensitive than conventional MRI sequences in identifying ictal and post-ictal changes. As we all know that neurological dysfunction following epileptic seizure is a well-recognized phenomenon and this is what forms the basis of post-ictal change. This may involve transient and reversible motor, behavioral and cognitive manifestations lasting from minutes to days. Which means that post-ictal changes may last for few minutes after the seizure episode or it may even last for few days after the seizure episode, making this little variable. Ideally, the typical findings on ASL are seen when the patient is imaged 20 to 60 minutes after the seizure episode, which might not be very practical in our day-to-day patients and we usually image patients in a time gap as early as 1 to 2 hours after the seizure episode. Coming to few examples to understand it better, here we see a patient who is 21 year old and presented with acute onset right-sided weakness. On diffusion, there was no area of restriction to suggest hyperacute or acute infarct. On flare images, however, there was relative hyperintensity seen in the left cerebral hemisphere. ASL colour maps clearly showed clear hypoperfusion in the left cerebral hemispheres, which was in keeping with post-ictal change. So, this was a case of TOTS paralysis. This patient was followed up after 24 hours gap and this hypoperfusion reverted back to normal. Another example, here also we can see that diffusion and T2 weighted images look almost normal. However, on ASL colour maps, there is clear difference between the right and the left and there is hypoperfusion in the left cerebral parenchyma or representing post-ictal change. Another example from pediatric age group T2 and diffusion normal, but ASL showing clear hypoperfusion on the right and that on EG as well correlated with the rectal focus. So, if we try to summarize, we can understand that ASL is a safe, feasible and cost-effective imaging modality that can be used in post-ictal period to assist with the localization of seizure onset zone. In most of the patient that is like in this study, 80% of the patient what is seen is hypoperfusion. Sometimes, yes, hyperperfusion is also seen, but in those scenarios, most of the times inter-ictal baseline activity is also there. So, in post-ictal states or phases, the most common finding with ASL is hypoperfusion at the site of rectal focus. ASL correlates well with the spec and pet finding. While on the other hand, it is totally non-invasive and very easily repeatable as compared to these two techniques that is spec and pet. Another interesting example, here we see a patient who is 22 years old and comes with an episode of seizure. Post-contrast even as well as the routine T2 weighted image do not show any obvious abnormality. However, on ASL color map, there is clear hypoperfusion in the right cerebral hemispheres. At the same time, we see hypoperfusion in the contralateral cerebellar hemisphere as well. So, this brings us to a very interesting phenomena of crossed cerebellar diastasis. This is a phenomena where there is acute inhibition of function and metabolism produced by a focal disturbance in a portion of the brain at a distance from the original site of injury but connected via white matter tracks. Here in this case, it is the corticoponto cerebellar white matter tracks which are involved. Another example where the routine T2 weighted images show us the actual cause of seizure in the form of focal cortical dysplasia and the corresponding ASL color maps are showing hypoperfusion in this region. Another example where there is a small focal cortical dysplasia which is the cause of seizures and here we can understand the fact that though the spatial resolution of ASL is low as compared to the conventional MRI sequences, still we can see the small area as hypoperfused in the post-dictal phase, again making our diagnosis more confident. And for those radiologists who are like quickly looking through the images, they can actually get ASL as an important technique and use it to pick up the abnormality on the corresponding MRI images of conventional MRI sequences. Another example, here we see a very small area of abnormality in the right posterior parietal cortex cortical region in the form of few flow voids. Tricks was also performed which is time dissolved imaging of contrast kinetics. Here we could see small abnormal cluster of blood vessels and this was seen as area blooming on swan images. When we see the corresponding ASL color map, though this area is so small, still ASL picked up hypoperfusion in this region. And on literature review, we were supported by the fact that yes, ASL can pick up these areas of small vascular malformations like dural AV fistulas and these are seen as areas of hyperperfusion. Another example where there is a kid 14-year-old presenting with features of right-sided focal dystonia and ASL was showing relative hyperperfusion on the left. And this has been described due to the recurrent dystonic episodes. There is recurrent activity and what we can see on ASL is hyperperfusion. So this is effect rather than cause of this particular condition. Moving next to role of ASL in CNS infections. Most of the infectious etiologies are hyperperfused like we see in this case of a brain abscess. It has typical features of brain abscess with restricted diffusion. Not very difficult to diagnose on routine MRI as well but yes ASL will definitely support our diagnosis by depicting hyperperfusion and limit the differentials. Another example a very small tuber coloma. This example emphasize on the fact that though the area of abnormality is small though it is in the posterior fossa still ASL is sensitive enough to show the hyperperfusion. This is very useful in cases of not an infection per se but in cases of metastasis to pick up small small mess in the brain. Especially in those patients where contrast is contraindicated. One more important aspect of ASL in imaging infection is viral encephalitis. So though all other infectious etiologies are known to be hyperperfused viral encephalitis most of the times are hyperperfused. So in these patients when there is clinical support to the diagnosis of encephalitis. Though the routine MR images may be normal if ASL is showing asymmetric hyperperfusion we should confidently inform our clinicians that there is a chance and possibility of viral encephalitis. Coming to the role of ASL in brain tumor imaging. As we all know that perfusion the concept itself came from tumor imaging. So the conventional MR sequences which are based upon contrast enhancement that is just secondary to disruption of blood brain barrier and that does not correlate with the tumor grade. All these tumors exhibit a phenomenon of new angiogenesis which is based upon the grade of the tumor and perfusion is something which can actually determine the grading of the new angiogenesis. Therefore perfusion techniques are ideal to diagnose and grade these tumors also to guide for biopsy to avoid sampling biases and also to follow these patients after treatment to diagnose a condition like pseudo progression and pseudo response. Coming to the examples here is a well-defined focal lesion seen in the right parietal parenchyma with perillegional edema. On post contrast evaluation it shows heterogeneous predominantly peripheral enhancement with an inner cremated margin which is a very typical of high grade tumors and on ASL we can clearly see that this area is hyperperfused. Even on the corresponding DSC color maps this area is hyperperfused both the perfusion techniques are correlating and this turned out to be GBM grade 4. Coming next to few more examples now this is a case of ependymoma showing patchy hyperperfusion so this is the area which should be biopsy to get the highest grade on histopath and to avoid sampling biases. Small oligoastrocytoma hyperperfused a small area of post treatment follow up patient with a small area of peripheral enhancement and irregular margins on ASL the area is completely hyperperfused and this was nothing but post radiation necrosis with no obvious residue. Another example a large heterogeneous signal intensity lesion with midline shift quite a lot of mass effect and perillegional edema but what ASL helps us is showing us the highest grade of tumor is along its anterior aspect and this is what should be biopsied. Interesting example of a patient who presented with patchy areas of altered signal intensities on T2 and flare images no contrast enhancement and ASL showing obvious hyperperfusions which are so evident as compared to the rest of the sequences this turned out to be primary CNS lymphoma. Here is an example of a patient who after TMZ that is Timozolamide and radiation therapy came for a follow up and showed a area of focal enhancement on post contrast study there was this enhancement but on ASL this area was completely hyperperfused so which means that this is nothing but a phenomena known as pseudo progression very well seen with Timozolamide and that the treatment should be continued. Not only for intraaxial lesions but ASL also can depict hyperperfusion in something like meningioma so even if you don't give contrast you can confidently diagnose meningioma with this kind of a picture of ASL. Coming to the role of ASL in dementia and psychiatric disorders as we all know that imaging nowadays play a very important role in imaging dementia patients and as well as their treatment work up so ASL is a potential technique which without contrast and by adding just a four minute extra to your protocol can give you information about the brain perfusion. In Alzheimer's pattern of dementia hyperperfusion is seen in cingulate pre-cumulus inferior parietal and later prefrontal cortisis or symmetric hyperperfusion may be seen in hippocampus amygdala and ventral stritum. In vascular kind of dementia we are going to see global hyperperfusion in frontotemporal dementia we are going to see hyperperfusion in frontal and temporal lobes. We can actually quantify the amount of cerebral blood flow in these patients of dementia the perfusion status on these color maps by drawing ROIs or region of interest. Coming to the role of ASL in autism and autism spectrum disorder there are several papers talking about it hyperperfusion in children with ASD in region critical to social perception and cognition have been described so period temporal sulcus hyperperfusion in children with autism spectrum disorder is what is commonly seen. Even in patients who have symptoms towards schizophrenia there are studies and this is our own patient where we can see hyperperfusion typically is described in the medial cingulate gyri and maybe in the parietal lobes. So to summarize all these pathologies where we have differential perfusion ASL is definitely important and a very easy way to help us in diagnosis. So like luxury perfusion cases of infarcts from politic induced recanalization post-tictal states sometime tumors as per their grade vascular malformation as one of the examples we saw of AV facial other than migraine inflammation encephalitis all of them viral encephalitis will be hyperperfused otherwise ischemic encephalomalacia post-tictal state most commonly as we saw hematoma infections vasculitis cerebral atrophy brain net patients will be hyperperfused there are few pitfalls and limitation to the technique in the form of that it is very prone to movement artifacts there is low signal to noise ratio that is why 3 tesla will be better than 1.5 tesla a minimum acquisition time of 3 minutes is required ideally we do it for 4 minutes 42 seconds here at our place quantification of tissue blood volume is not possible and post treatment optimization automation and standardization is still in development there are few things which are going to come up in recent future maybe and help us like ASL in assessment of whole lateral circulation so we are going to actually see arterial territory wise perfusion status of the brain combination of DTI with ASL as a marker of early Parkinson there are studies going on again use of ASL in functional MRI assessment so a lot of things to be seen in future even ASL is coming up for abdominal inmiching to assess abdominal perfusion so ASL is non-invasive suitable for perfusion in patients wherever contrast is contraindicated safe in pediatric population repeatable easy add on to our protocols can be quantitative can assess global perfusion states and definitely add confidence to our diagnosis thank you all for your patient listening