Wk8 RNI-Brain and Renal Scans PDF

Radionuclide Imaging (RNI) HTI 48102 Brain and Renal Scans Liang-Ting Lin  The rst and second ventricles are lateral ventricles. These C-shaped structures are located beneath the cerebral cortex,...

Radionuclide Imaging (RNI) HTI 48102 Brain and Renal Scans Liang-Ting Lin  The rst and second ventricles are lateral ventricles. These C-shaped structures are located beneath the cerebral cortex, the wrinkly outer layer of your brain. Usually, the lateral ventricles are symmetrical. But between 5% and 12% of the population are anatomically di erent, with one side larger than the other. When this happens, it's usually the left side that's larger.2 The third ventricle is a narrow, funnel-shaped structure situated between your right and left thalamus, just above your brain stem. The fourth ventricle is a diamond-shaped structure that runs alongside your brain stem. It has four openings through which cerebrospinal uid Brain Scans drains into an area surrounding your brain (subarachnoid space) and the central canal of your spinal cord. CSF takes the following route through the four ventricles of the brain:3 Central Nervous System The walls of the lateral ventricles and the roofs of the third and fourth ventricles are lined with a layer of specialized tissue known as the choroid plexus. It's within the choroid plexus that CSF is produced. CSF passes from the lateral ventricles, through two holes called the interventricular foramina, and into the third ventricle. From there, CSF passes through a connecting structure called the cerebral aqueduct and into the fourth ventricle. CSF exits the fourth ventricle and drains into the subarachnoid space. CSF also passes through a structure called the obex before draining into the central canal of the spinal cord.  Brain – Central Nervous System ˇ uses of ventricle: produce and secrete cerebrospinal uid to protect and maintain your central nervous system bundle of nerve bre for left and right communication a thin, triangular, vertical double membrane separating the anterior horns of the left and right s lateral ventricles of the brain. It runs as a sheet from the corpus callosum down to the fornix. foramen-> allow passage bre motor and cognitive vital function  Brain – Indications Planar brain imaging 2D A I Bilateral To use radiopharmaceuticals that are perfusion agents and do not routinely cross an intact blood-brain barrier iiiiǎinateniiii9点 Usually performed for brain death studies SPECT imaging 3D fat loving To use lipophilic radiopharmaceuticals that routinely cross the blood-brain barrier to localize in normal/pathologic brain tissues/functions Visualizing regional cerebral blood flow (rCBF) PET imaging itiiggeringsenure tobefore or after To use functional radiopharmaceuticals reflecting metabolic and neurotransmitting events hrennactiuty iiiiiiiiiiiiiii器  Planar brain imaging – Radiopharmaceuticals Dynamic angiographic imaging tosurrogatehloodiupplyonly Bolus injection – rapid sequential images of the arrival of radiotracers lack of A measure of transient cerebral perfusion nmnaiw in 㗊 毕 1 因 1四 i no pasnq 99mTc-DTPA (diethylenetriamine pentaacetic acid) 㗊 veslen 99mTcO4 (Pertechnetate) Delayed static (perfusion) imaging nn.nuupount l.inniii 品 aaiiiǐiiiiiiiiiiiiiin hydrophobic Lipophilic perfusion agents – brain extraction low duie patiinl 品了 iii品 A measure of tissue uptake and active functioning enetrete ii 3 99mTc-HMPAO (hexamethylpropyleneamine oxime) 99mTc-ECD (ethylene l-cysteinate dimer)x y ǐiǎiitiii P ǐass thmB.B. óii isr.in Paǎnniog 4memhvene phospholipidlayer  Blood Brain Barrier A barrier of brain capillaries to defend brain from circulating toxins Only water and essential elements (gas) can penetrate Essential chemicals or substances must be transported through the polarized cells Integrity of BBB is reduced in some pathological scenario icnnvlletthugeeec.ly essentiihtiaittrm innyguvinoriverytight receptor paenttm 1cell CRBB 4 otherbodypan channel 1 at notthatlinecanpass thru Liphophnhcbyihancecan passthru it 4smallfractionofdrugscan CMT: Carrier-mediated Transportation; RMT: Receptor-mediated Transportation enter Xiao M, Xiao ZJ, Yang B, Lan Z and Fang F (2020) Blood-Brain Barrier: More Contributor to Disruption of Central Nervous System Homeostasis Than Victim in Neurological Disorders. Front. Neurosci. 14:764. doi: 10.3389/fnins.2020.00764  The principles of Brain RNI iiǔi品品 The presence of BBB makes brain a unique organ Neurons do not have intracellular metabolic stores and thus require continuous supplies of oxygen and glucose The increase of blood flow/perfusion surrogate the neuronal activities The disruption of BBB -> pathologic findings The absence of blood flow/perfusion -> brain death  Planar cerebral imaging – 99mTc-DTPA giiiiiunno iiii in Technetium-99m diethylenetriamine pentaacetic qniiiǐüiiiisiniiiitina acid (DTPA) more quǎiiihiiiiǎüncce 99mTc-DTPAis an inexpensive chelator used primarily for dynamic renal and brain imaging Pharmacokinetics after injection-> drugs distribute Rapid extravascular distribution by vessel very quickly Cleared by glomerular filtration (kidney, hydrophilic) 5%-10% plasma protein binding bounded= cannot cross the membrane-> a ect e cacy Radiation dose at bladder (27 mSv/370MBq) Hydration and frequent voiding  piiiiiniiiniinniǚ Patient positioning – as close as possible 2hm.nntn.mu ǚiiii蘂器器 nmǎlisurtpctnent weirdactingat cerondartery  Planar cerebral imaging – 99mTc-DTPA Another meaning: The trident sign nrltng initially (a.k.a. omega sign) describes the I typical appearances of the pons Collimator: LEHR in osmotic demyelination syndrome Patient position: Supine Dose: 15-30 mCi (555MBq – 1.11GBq) Imaging setting: Dynamic image – Anterior view Static image – Ant., Post., and both laterals (300k counts per view) Imaging features: 三腳叉gum Middlelaqidteng u sign (MCA) Symmetric perfusion – Trident calvarium is the convexity of the skull and encases the brain parenchyma Perfusion extends to calvarial convexity Asymmetry may appear due to variations in venous anatomy  exkriien Planar cerebral imaging – 99mTc-DTPA Collimator: LEHR Patient position: Supine Imaging setting: Dynamic image – Anterior view 10 Static image – Ant., Post., and both laterals (300k counts per view) iiier net 台ǎǐyeiblǎǐiriiǐiiu Imagine features: No apparent accumulation in brain Overlying in scalp soft tissues, calvaria, and subarachnoid spaces consists of the cerebrospinal uid (CSF), major blood vessels, and Sinuses accumulation noted cisterns, separation of arachnoid mater and pia mater http://www.people.vcu.edu/~mhcrosthwait/clrs319web/Brainimagingpart%20I.htm  Planar cerebral imaging – 99mTc-DTPA Collimator: LEHR Patient position: Supine Imaging setting: Dynamic image Static image Indications: BBBxwovliing hu udtelie Stroke (luxury perfusion) Brain tumor langersnybrecl 131313 Hemorrhage Cerebral vascular accidents In a sense of NEGATIVE scan Stroke GBM glioblastoma-> brain cancer penetnle orlywher patient death ncyhu.BBB  Brain Death scan – 99mTc-DTPA iiàiinninniidininǐtiii n.uppn.n.t.in Lack of intracranial arterial flow The carotid arteries are visualized in the neck, but there is an abrupt cut- off of activity at the skull base Sagittal/Venous sinuses are not visible on subsequent static images totǎlynoblood The hot nose sign supplyto brenn Due to increased flow in the why external carotid circulation. No cerebral or cerebellar accumulation of the radiotracer  Brain perfusion scan – 99mTc-ECD / 99mTc-HMPAO 99mTc-Hexa-Methyl-Propylene-AmineOxime 99mTc-Ethylene-L-Cysteinate Dimer BBB penetrating (lipophilic) First-pass extraction in Gray Matters Demonstration of brain activities iǎiǐi品 Brain death scan – static imaging Brain perfusion scan – tomographic imaging sleepis mnreǎnttǎnniy Administration instruction: dunsleep Place patient in a quiet, dimly lit room and instruct him or her to keep eyes and ears open. 斜躺 The patient should be seated or reclining comfortably. IV access should be placed at least 10 minutes before injection inniiiiéniiniǎiiiii The patient should not speak or read, and there should be little or no interaction before, during, or up to 5 minutes after injection. https://collection.sciencemuseumgroup.org.uk/objects/co454593/ceretec-used-as-diagnostic-to-visualise-blood-flow-in-the-brain-1988-1998-diagnostic-imaging-agents  Brain perfusion scan – Minimal Brain Stimulation Aim at standardize and controlled environmental conditions and patient status. Explain the whole procedure to patient including the pre-injection procedure and emphasize the importance of immobility during imaging. Allow the patients to rest in supine posture for at last 15 minutes with eyes open and ears unplugged. Background noise should remain the same for all studies/scans and the ambient light should be dimmed.  Brain perfusion scan – 99mTc-HMPAO Greymatter normal image Collimator: LEHR Patient position: Supine Dose: 15-30 mCi Imaging setting: Delayed phase – 45 mins to 4 hrs Indications: Abnormalactivity in Brem Epilepsy abnormal brain electrical activity Dementia aAlzheimer's general term-> e.g. is disease Brain death early brain decay of nerve cells in the Huntington’s disease key part of the network of brain cells and nerves that control your body's voluntary movements, Basal ganglia disorders which is controlled by grey matter too-> white matter is act as a Cerebrovascular diseases transmitter and body between GM and GM Cerebral vasomotor reserve the vasodilation capacity of cerebral ^Planar imaging arterioles to external stimuli  Brain Death scan – 99mTc-HMPAO Indications for Brain Death Scan If components of neurologic mental status and level of consciousness, pupillary response, motor strength, sensation, and gait. examination cannot be performed or results are uncertain response to increase in CO2 If apnea test cannot be performed To shorten duration of observation period If uncertain medication effect is present If helpful for family members to better comprehend diagnosis similar  Epilepsy scan – 99mTc-HMPAO More aiureie hyspi17 09 iii.i.in'eaineyreleeudelenihel Epilepsy is one of the most prevalent neurological disorders. Seizures can be classified as either partial (focal) or generalized About 10-20% of patients with partial complex seizures have inadequate control on medical treatment _eleltnesrndihmmonitor Scalp EEG often fails to accurately localize the seizure focus Depth EEG is more accurate but extremely invasive and suffers from regional under-sampling CT and MRI have low sensitivity for seizure foci detection, 17% and 34% respectively  Epilepsy scan – 99mTc-HMPAO All SPECI Xplenar Detection of intensive metabolic function To localize the epileptic lesion Hypoperfusion Pre-/post- seizures, blood flows decrease Ictal hyperperfusion nuptekemweblood During seizures, blood flow increases inn in irecie At least Two views required Ictal + interictal Peri-ictal + interictal stnunng  shnnllagt meteb.ly 器ndevn freilytuens.to Metabolic (tumor) imaging – 18F-FDGBBB no verellhvenaitnntyt foralzheimer Collimator: No (PET) 即 品品itcǐǐiune Patient position: Supine Dose: 10-20 mCi (370-740 MBq) Imaging setting: Time: 60 minutes after i.v. Short half-life 110mins Preparation: to lower their blood sugar level so Fast for >4 hours that FDG would not compete with glucose for its transporters for tumor uptake during the PET Suspend insulin dosing scan. Patient rest for >30 mins CT scan is compulsory tpiiimus1 Alzheimer’s Disease Neurodegenerative disease o.RTfr.li 24  Alzheimer’s Disease An illness resulted from neurodegeneration Brain atrophy Irreversible brain damage in loss of memory (dementia) and mental health motor fbi1 Causes of AD is still unknown Major issue in modern public healthcare Early detection is critical No effective treatment available currently 25  hypothenc only Cause of Alzheimer Disease Amyloid hypothesis : Aβ monomer -> Soluble oligomers (2-6 buthaveAβ peptides) -> Amyloid plaques (insoluble fibers) -> Disrupted haechtenner no Neurotransmission rmel L L 蕊wtd 0 ndegvadahl P 9I iiniinhre forever Hey cuianglnnmi xnnnngn Occasionally happened dt.nnm.ingini něiaiiiinin whichenrym to dothedyethn the enzymes are in helena 煎意器nu 27 Heppner, F. L., Ransohoff, R. M. & Becher, B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 16, 358-372, doi:10.1038/nrn3880 (2015).  AD diagnosis – A detection indicates early stage ng nonlyeúiung here tseni.hu.th mild cognitive impairment 28 Cohen, A. D. & Klunk, W. E. Early detection of Alzheimer's disease using PiB and FDG PET. Neurobiol Dis 72 Pt A, 117-122, doi:10.1016/j.nbd.2014.05.001 (2014).  PIT 11C-PiB imaging – A distribution related to AD tveiev nu 嵧然 Info10 11C-PiB is a carbon-11 labeled Cnfeli compound that binds speci cally to amyloid-beta (Aβ) aggregates. hmiletmi rll71lenu to PiB Aizenstein, H. J., Nebes, R. D., Saxton, J. A., Price, J. C., Mathis, C. A., Tsopelas, N. D., Ziolko, S. K., James, J. A., Snitz, B. E., Houck, P. R., Bi, W., Cohen, A. D., Lopresti, B. J., DeKosky, S. T., 29 Halligan, E. M. & Klunk, W. E. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 65, 1509-1517, doi:10.1001/archneur.65.11.1509 (2008).  11C-PiB imaging – A distribution vs. MRI MRI not much di... PET is more sensitive Okamura, N., Harada, R., Furukawa, K., Furumoto, S., Tago, T., Yanai, K., Arai, H. & Kudo, Y. Advances in the development of tau PET radiotracers and their clinical applications. Ageing Res Rev 30 30, 107-113, doi:10.1016/j.arr.2015.12.010 (2016).  18F-FBP mwlntiddny 1 1imaging – A diffuses in grey matters No pathologic findings Suspected AD 31  dical Agency the risk of AD by one-third, the findings authors also demonstrated that F-THK5105 amyloid-PET that corroborate the long prodromal phase in retention correlated positively with dementia rocedure that D from other AD imaging – the current available targets AD suggest that secondary prevention—for example, anti-amyloid therapies (currently severity, as defined by the Clinical Dementia Rating Assignment score, and inversely with ging markers CSF Aβ1–42 s to incorpo- CSF tau CSF p-tau Cerebrospinal uid agnostics—an nal Working Extracellular Neuron brillar Aβ plaques ional Institute Tau iation (NIA– Intracellular oligomeric Aβ n The Lancet G proposed a Synaptic failure Neurodegeneration rch diagnos- track integrity myelin integrity in es in the brain cerebral white matter (WM) F13可 els of Aβ 1–42, PiB–PET 18 F-THK5105–PET 18 F-FDG–PET MRI 18 F- orbetabir–PET 18 F-T808–PET I horylated tau A targeting 18 F- orbetaben–PET 18 F-PBB3–PET Tau targeting hypo-metabolism l fluid (CSF) 18 F- utemetamol–PET 18 F-THK5117–PET ophysiological Presymptomatic Prodromal Alzheimer disease Alzheimer dementia false positive tproblen io urodegenera- st, 2014) Amyvid, Eli Lilly (1 Figure 1 |Factors contributing to AD pathology. the Accumulation annual incidenceof of misfolded Aβ and healthy subjects Nature tau oligomers becoming Reviews amyloid scan | Neurology deoxyglucose phy quantified npnh inNeuraceq, neurons isPiramal thought Imaging Vizamyl, GE healthcare neurodegeneration. to underlie Novel (2 nd rd (3 the , 2014) , 2014) imaging positive, asof pathophysiology evaluating reported elderly in a recent AD leading subjects, was study from to synaptic estimated the Mayo failure to be andClinic, 13% methods (such as tau visualization) can facilitate understanding per year onsidered as a of the longitudinal course of AD and identification of individuals who are in the earliest stages of the 32 1 Nordberg, A. Dementia in 2014. Towards early diagnosis in Alzheimer disease. Nat Rev Neurol 11, 69-70, doi:10.1038/nrneurol.2014.257 (2015).  enthusiasm finalized.) with the fact that we’re gotten solanezumab or placebo in 2,100 people with the extra information people think they can these Without agents the added tomarket the point where they’re boost of insurance early-stageFDA- Alzheimer’s disease.Head to head: Vizamyl process,PET images ” Brophy of athey says. Now, healthy just have brain to (left) and a © 2013 Nature America, Inc. All rights reserved. approved, ” says peopleDavid in the Wolk, a neurologist at imaging agents for convince insurers and the medical community the coverage, most Vizamyl A imaging – not conclusive for AD diagnosis to make a difference University field expect mainly in clinicalin Philadelphia of Pennsylvania Studies involving Alzheimer’s, as they grow agents inNsizeEWand are S length, that that information is clinically meaningful. already poised to have a larger impact. of the amyl trials. But many believe the two new imaging could ultimately be used to support the approval Sarah CP Williams who was involved in clinical trials of Vizamyl. In a recently published set of best-practice as diagnos Alzheimer’s imaging agents struggle to find a market outside trials “Having more options will certainly move the guidelines on the use of amyloid PET imaging, Nprogression EW S Physicians in the US whoNATURE want to see how much VOLUME 19 | NUMBER 12 | DECEMBER 2013 amyloid-beta proteinfield forward. has accumulated in the ” MEDICINE Dean Hartley, director of science initiatives at 1551 additional s brains of their patients with Alzheimer’s disease now have two options of imagingHowever, agents. On 25 these new options still have their Alzheimer’s imagingthe agents Alzheimer’ struggle to find a market s Association in Chicago, outside and trials amyloid to October, the US Food and Drug Administration (FDA) announced the limitations. approval of Vizamyl Both imagingPhysicians agents in thehave US who want beento see how much a team of other scientists from around the require suc (flutemetamol F-18), a positron emission amyloid-beta protein has accumulated in the granted tomography (PET) radiotracer only that binds to narrow approval: brains of thetheir compounds patients with Alzheimer’s disease US suggest that the imaging agents are well- Neverthele amyloid plaques, the abnormal brain deposits can’t that are thought to cause be used to definitively diagnose neurodegeneration. Alzheimer’s studied enough that they can be used in clinical bring imag now have two options of imaging agents. On 25 October, the US Food and Drug Administration Vizamyl, developed by UK-headquartered GE Healthcare, joins disease or to gauge treatment(FDA) a similar diagnostic effectiveness, only settings to help diagnose patients with early eventuality announced the approval of Vizamyl (flutemetamol F-18), a positron emission compound for Alzheimer’s disease called Amyvid (florbetapirto support F-18), which received other diagnostictomography criteria.(PET) radiotracer that bindsonset to of Alzheimer’s or unusual symptoms of Ohio-based GE Healthcare approval last year. amyloid plaques, the abnormal brain deposits “I think there should Some be a great deal enthusiasm with the fact that we’re gotten studies of have found that amyloid are thought to cause buildupneurodegeneration. disease (Alzheimers Dement. 9, e106–e109, imaging age Vizamyl, developed by UK-headquartered in where these agents to the point elderly people they’re FDA- Head towith allPETtheir head: Vizamyl mental GE ofHealthcare, images faculties; a healthy brainjoins (left) a similar and 2013). diagnostic an Alzheimer's brain (right). In these cases, the battery of cognitive 3 trials, and © 2013 Nature America, Inc. All rights reserved. approved,” says David Wolk, a neurologist at compound for Alzheimer’s disease called others the University of Pennsylvania have agents in Philadelphia shown that are already poised to havethe toxicof theprotein a larger impact. Amyvid (florbetapir amyloid imaging agents F-18), which received who was involved in clinical trials of Vizamyl. In a recently published set of best-practice as diagnostic tools or a way to track disease tests clinicians for broader use rely on for diagnose can lead to based Piram GE Healthcare approval last year. accumulates Dean in Hartley, other forms“I initiatives ofthinkdementia. aSo, “Having more options will certainly move the guidelines on the use of amyloid PET imaging, progression. What’s needed to take that step are field forward.” director of science there should be at additional studiesgreat dealmixed of link changes that definitively results, in and the scans could help clarify with both U for now, the FDA has ruled these limitations. Both imaging agents have been a team of other scientists from enthusiasm thataround with a negative the to therequire the fact that scan we’re However, these new options still have their the Alzheimer’s Association in Chicago, and amyloid to treatment success—but that will first agents pointsuccessful where they’re gotten diagnosis, FDA- treatments to be Head developed. treatment options and prognosis. to head: Vizamyl PET images of a healthy brain (left) and an Alzheimer's brain (right). All thes rica, Inc. All rights reserved. in diagnose someone Alzheimer’s with cognitive granted only narrow approval: the compounds US suggest that the imagingapproved, impairment agents are” well- says David can inagents Wolk, amore Nevertheless, be neurologist “We companies think at are hoping to there is a specific population that can called thiof it iiiiiii 器 in set of best-practice as diagnostic tools or a way to track disease uiǐimi can’t be used to definitively studied enough that they can the be used bring imaging in clinicalof Pennsylvania University to market today Philadelphia for are agents the already poised to have a larger impact. of the amyloid imaging agents for broader use npg used to point clinicians toward disease or to gauge treatment effectiveness, only settings to help diagnose patients to support other diagnostic criteria. onset of Alzheimer’s or unusual who wasother with symptoms “Having involved incauses early moreofoptions eventuality of clinical trials Ohio-based of wider gain approval. of Vizamyl. For Navidea Biopharmaceuticals will certainly Infrom example, move the guidelines a recentlyhaving published this has an on the use of amyloid PETability to detect amyloid,” structures imaging, progression. What’s needed to take that step are Hartley says.director of science initiatives at additional studies that definitively linkradioisotop in elderly people withdementia, while a these positive scan remains more Some studies have found amyloid buildup disease (Alzheimers Dement. 9, e106–e109, imaging agent called NAV4694 in ongoing phase field forward. ” Dean Hartley, changes in all their mental faculties; 2013). In cases, the battery of cognitive 3 trials, and florbetaben, developed by Berlin- However, these new options still have their the Alzheimer’ s Association in Chicago, and amyloid to treatment success—but that will first niii in others have shown that the toxic protein tests clinicians rely on for diagnose can lead to based Piramal Imaging, is currently under review ambiguous. limitations. Both imaging accumulates in other forms of dementia. So, mixed results, and the scans could help clarify with both US and EU regulators. agents have been a team of other scientists from around the require successful treatments to be in a PET sc developed. for now, the FDA has ruled that a negative scan diagnosis, treatment optionsgranted only narrowAll and prognosis. approval: 了 USof suggest the compounds these compounds—variants a dye that the imaging agents are well- Nevertheless, more companies are hoping to 33 in someone with cognitiveIn light impairment of “We can be the thinklimited there is a specificdiagnostic can’t be used population utility to definitively that can called diagnose thioflavin of Scanning Alzheimer’ T, which binds studied enough sbeta-sheet-rich the horizon that they can be used in clinical bring imaging agents to market today two approv for the  coniluinm A imaging – Amyvid® prescribing info 34  Cause of Alzheimer Disease insoluble aggregates called neuro brillary tangles. Tau Hypothesis : Tau protein hyperphosphorylation roles primarily in maintaining the disionneihmit stability of microtubules in axons and are abundant in the neurons neuwne of the central nervous system (CNS), where the cerebral cortex has the highest abundance 35  dical Agency the risk of AD by one-third, the findings authors also demonstrated that F-THK5105 amyloid-PET that corroborate the long prodromal phase in retention correlated positively with dementia rocedure that D from other AD imaging – the current available targets AD suggest that secondary prevention—for example, anti-amyloid therapies (currently severity, as defined by the Clinical Dementia Rating Assignment score, and inversely with ging markers CSF Aβ1–42 s to incorpo- CSF tau CSF p-tau Cerebrospinal uid agnostics—an nal Working Extracellular Neuron brillar Aβ plaques ional Institute Tau iation (NIA– Intracellular oligomeric Aβ n The Lancet G proposed a Synaptic failure Neurodegeneration rch diagnos- es in the brain els of Aβ 1–42, PiB–PET 18 F-THK5105–PET 18 F-FDG–PET MRI 18 F- orbetabir–PET 18 F-T808–PET horylated tau A targeting 18 F- orbetaben–PET 18 F-PBB3–PET Tau targeting l fluid (CSF) 18 F- utemetamol–PET 18 F-THK5117–PET ophysiological Presymptomatic Prodromal Alzheimer disease Alzheimer dementia urodegenera- deoxyglucose Figure 1 |Factors contributing to AD pathology. Accumulation of misfolded Aβ and Nature tau oligomers Reviews | Neurology in neurons is thought to underlie the pathophysiology of AD leading to synaptic failure and phy quantified neurodegeneration. Novel imaging methods (such as tau visualization) can facilitate understanding onsidered as a of the longitudinal course of AD and identification of individuals who are in the earliest stages of the 36 1 Nordberg, A. Dementia in 2014. Towards early diagnosis in Alzheimer disease. Nat Rev Neurol 11, 69-70, doi:10.1038/nrneurol.2014.257 (2015).  THK5117 imaging – Tau protein distribution antibody recognizes and binds phosphorylated epitopes of the Ta iinennnnnu ctPhospho-Tau 品 Tau protein (PHF-Tau). This antibody does not cross react with normal Tau or bovine Tau. protein 37 Saint-Aubert, L., Lemoine, L., Chiotis, K., Leuzy, A., Rodriguez-Vieitez, E. & Nordberg, A. Tau PET imaging: present and future directions. Mol Neurodegener 12, 19, doi:10.1186/s13024-017-0162-3 (2017)  18F-THK5117 imaging – Tau protein in AD patients ntn killed BetterSNRthen to track the neuro brillary tangle!!! Aβ Okamura, N., Harada, R., Furukawa, K., Furumoto, S., Tago, T., Yanai, K., Arai, H. & Kudo, Y. Advances in the development of tau PET radiotracers and their clinical applications. Ageing Res Rev 38 30, 107-113, doi:10.1016/j.arr.2015.12.010 (2016).  AD imaging – FDG is used for diagnosis FDG is used for initial examination – decreased glucose uptake indicates less activity rholehiiiǎji品 lenurldnfferentiele where 39 Cohen, A. D. & Klunk, W. E. Early detection of Alzheimer's disease using PiB and FDG PET. Neurobiol Dis 72 Pt A, 117-122, doi:10.1016/j.nbd.2014.05.001 (2014).  AD imaging – Tau protein signals eavlystegl redis higher Befeerni i in n1 AP_ about the energy....dose... and better SNR Isup diagnrn AD everywhere have uptake-> normal 40 Saint-Aubert, L., Lemoine, L., Chiotis, K., Leuzy, A., Rodriguez-Vieitez, E. & Nordberg, A. Tau PET imaging: present and future directions. Mol Neurodegener 12, 19, doi:10.1186/s13024-017-0162-3 (2017)  AD imaging – Tau protein signals (AV1451) Mildsongmine 7mpcnuemnt iǒǐiyn 品 管 more cheferenu L chstingunshmerl Tau protein give better SNR sobrighterfuture 41  No Hurdles – Diagnostic value? Refrosyeitne to c treee back true positive true negative nrlevenbetterthanAβ 43 AD research now faces questions oiǐiiǎn findfake  The volume of plasma that Renal Scan passes through the kidneys per unit time, e ectively reaching the renal tubules for ltration. It re ects how e ciently the kidneys can clear substances from the plasma. E ective renal plasma ow (ERPF) can be measured by infusion of p- aminohippurate (PAH). PAH is secreted with high delity by the proximal tubule cells, with most cleared by a single pass through the kidney when infused at a low concentration, thus approximating ERPF.  Kidneys and the Urinary Tract ngyiitiǎiiiimiating Functional Study rouotttǎii 叫 Glomerular Filtration Rate (GFR) 器 excretedthunrechcwptiuii Effective Renal Plasma Flow (ERPF) Renography – time-activity curve Structural/Mass Study secrete waste products and excess water. and reabsorb useful stu deliver blood to the interlobar veins Renal cortex Morphology shorter longer-> water reabsorption Image foreshortening NOT ideal for size measurement collecting duct useus.v https://doctorlib.info/physiology/medical-physiology-molecular/34.html  Kidney Fact Sheet detail look at the tubule Excretory function of the kidneys it can do secretion... Passive filtration through the glomeruli (20%) Normal GFR: 120 ml/min Effective renal plasma flow (ERPF): 600 ml/min Filtration fraction: 20% Mostly reabsorbed Active secretion by the tubules (80%) Two layers in parenchyma Cortex – outer layer Medulla – interior core Approximate 20-25% of cardiac output goes through kidneys Resting cardiac output: 5L/min Resting kidney output: 1.2L/min  Indications for Functional Studies Assessment of renal function ditiiiitt Evaluation of a renal transplant Evaluation of acute renal failure 1. 99mTc-DTPA: Glomerular Filtration 3. 99mTc-MAG3: Tubular Secretion in stmituvel the e DMSA stay in irrtex i can see step ltration vs secretion glomerulus vs tubule and collecting duct remove waste and form urine vs adjust nal composition concentration (di. ions...)  Renal Scintigraphy Positioning Supine position recommended nntóiii器 Posterior view preferred mnǐ Anterior view is helpful occasionally Single camara is sufficient X Posterior view with a large FOV Morphological abnormality – horseshoe kidney – anterior view required used both kidney will change position Cystectomy – removal of bladder Kidney transplantation niiiiotcn included incnìiiici ii只照 https://www.poole.nhs.uk/a-z-services/n/nuclear-medicine/diagnostic-nuclear-medicine/renal-static-dmsa-scan.aspx  Glomerular Filtration Agents – 99mTc-DTPA Technetium-99m diethylenetriamine pentaacetic acid (DTPA) 99mTc-DTPA is an inexpensive chelator used primarily for dynamic renal and brain imaging Pharmacokinetics easilyobtained Rapid extravascular, extracellular distribution 9 Cleared by glomerular filtration 5%-10% plasma protein binding Renal perfusion imaging at first-pass Renal function imaging at delayed phase ifproblem??? didnt pass thru-> Radiation dose at bladder (27 mSv/370MBq) Hydration and frequent voiding  Tubular Secretion Agent – 99mTc-MAG3 Technetium-99m–labeled agent mercaptoacetyltriglycine (MAG3) 1dmuse MAG3 is a chelate for 99mTc. It is physio- logically analogous to 131I-hippuran but has favorable dosimetry and better images stick to plasma protein-> a ect the distribution? 90% Protein bound and is cleared predominantly secretion (active) (passive) by the proximal tubules (95%) with minimal filtration (less than 5%) fraction of a substance that is removed from BetterthenDIPIt the plasma as it passes through the kidneys Extraction fraction of 40% to 50% (about twice of 99mTc-DTPA), it provides more satisfactory images than 99mTc-DTPA uiiiioeuluu effediurenel pleemeflor  ovurell Pharmacokinetics – 99mTc-MAG3 preferredw Cleared mostly by tubular secretion – useful for effective renal plasma flow (ERPF) measurement (correction factor required) Minimal glomerular filtration (5%) Agent of choice in patients with renal insufficiency. Provides better images because it is not GFR dependent. Radiation dose at bladder: 48 mSv/370MBq higher then of DTP Takilngertoexirehonttofeelu.ge u.we 99m 99m Tc-MAG3 is preferred over Tc-DTPA in patients with suspected obstruction and impaired renal function and is used in approximately 70% of the renal scans performed in the United States tubular function and renal perfusion.  Radiopharmaceuticals – an ideal renal function agent ERPF agent is completely removed from plasma during its passage through the kidney (high first-pass extraction) MAh3 GFR agent is freely filterable by the glomerulus the size is smaller Agent is not protein bound. Agent is not metabolized. remain unchanged not broken down-> some changed component excrete by secretion -> reduce ltration No significant excretion by other organs occurs. a ect the calculation ERPF and GFR can be determined by 1. plasma sample-based clearances, which are more tedious but more accurate 2. camera-based clearances, which do not require sampling of plasma or urine we studying this.  Patient preparation Iiiǐniniinnronnm iiiiiiiiin.ie Adequate hydration is required for renal function studies iiiitiince Dehydration may delay the intraparenchymal transition and excretion eycreem Before acquisition, patients must void bladder Supine position – less thickness, more stable, better orientation A large FOV gamma camera with LEHR (or LEAP) collimator is used Anatomical landmarks with the help of a radioactive point source: Upper margin – xiphoid process should be in the proximity of the upper edge Center – the space between the iliac crest and costal arch Lower margin – the pubis should correspond to the lower portion In case of transplanted kidney evaluation, the detector must be positioned anteriorly centering the pelvis, because in these patients the kidney is in the iliac fossa Blood Flow Phase – bolus injection renclhyperlmnn iiǎiualndnes riǎii 7 Fronbech R 0  Blood Flow Phase – Transplanted kidney