Nephrolithiasis: Ultrasonography versus Computed Tomography

Written by: Kishan Ughreja , MD (NUEM ‘23) Edited by: Ade Akhentuamhen, MD (NUEM ‘21)
Expert Commentary by: Tim Loftus, MD, MBA

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Journal Club: Ultrasonography versus Computed Tomography for Suspected Nephrolithiasis

A 70-year-old man with BPH s/p TURP, hypertension, hyperlipidemia and stroke presents to the ED with acute onset of intermittent sharp left flank pain radiating into the groin that awoke him from sleep. He endorses nausea without vomiting and denies fever. He also endorses slightly decreased urination with “dribbling.” His urinalysis shows >100 RBC and no signs of infection. Nephrolithiasis is likely high on your differential diagnosis. How do you proceed?

What is your initial imaging test of choice, ultrasound (US) or non-contrast CT, and why?

Would you be satisfied with only US and no follow-up CT?

Would you be confident in a point-of-care-ultrasound evaluation or a formal ultrasound?

Do outcomes for patients with suspected nephrolithiasis differ based on the initial imaging?

Should your medical decision-making change if the patient has a history of nephrolithiasis?

What would you do if the same patient presented again with persistent pain from a previously diagnosed stone?

Pain from suspected nephrolithiasis is a very common complaint in the ED and the incidence of the disease continues to increase. The estimated incidence over the past two decades is up to 340 visits per 100,000 individuals.1 Low-dose non-contrast abdominal CT has become the gold standard for diagnosis as it has become readily available in emergency departments nationwide, with some studies touting sensitivity and specificity of 97% and 95%, respectively.2  However, low dose CT still exposes the patient to radiation and may increase their risk of cancer, as many nephrolithiasis patients often undergo repeat imaging because of recurring pain or urological intervention. Additionally, CT scans prolong average ED lengths of stay.  However, with ultrasonography becoming more prevalent in EDs, it may be possible that initial imaging may avoid this radiation risk and still have similar outcomes for patients. Let’s analyze this NEJM article comparing US to CT for the assessment of nephrolithiasis.

Study design: a multicenter, pragmatic, randomized comparative effectiveness trial

Population

• N = 2759

• ages 18- 76 yo

• reported flank or abdominal pain that the treating physician wished to order imaging to establish or rule out a primary diagnosis of nephrolithiasis

• not considered at high risk for serious alternative diagnoses e.g. cholecystitis, appendicitis, aortic aneurysm, or bowel disorders

• no pregnant patients

• no men >129 kg, no women >113 kg

• no history of single kidney, renal transplantation, undergoing dialysis

Patient selection

Intervention protocol

• patients randomized to 3 groups each using a different initial imaging modality (POCUS vs. Radiology US vs. CT)

• patients contacted at 3, 7, 30, 90, and 180 days after randomization to assess study outcomes

Outcome measures

Primary Outcomes

• high-risk diagnoses with complications that could be related to missed or delayed diagnoses — within 30 days of ED visit, including:

• AAA w/rupture, PNA w/sepsis, appendicitis w/rupture, diverticulitis w/abscess or sepsis, bowel ischemia or perforation, renal infarction, renal stone w/abscess, pyelonephritis w/urosepsis or bacteremia, ovarian torsion w/necrosis, aortic dissection w/ischemia

• cumulative radiation exposure from all imaging within 6 months after randomization

• total cost (not reported in this study, ongoing analysis)

Secondary Outcomes

• serious adverse events (FDA definition) 

• serious adverse events related to study participation

• delayed diagnosis, like acute cholecystitis, appendicitis, bowel obstruction

• return ED visits

• hospitalizations after being discharged from ED

• self-reported pain scores

• diagnostic accuracy for nephrolithiasis

• by comparing ED diagnosis at discharge to reference standard of confirmed stone by patient’s observation of passage or report of surgical removal

Results

• no significant differences among groups in terms of pain scores, medical history, physical exam findings, and ED physician’s assessment of the likelihood of other diagnoses (Table 2)

• POCUS and US groups had significantly lower cumulative radiation exposure over 6 months than the CT group (difference attributed to initial ED visit’s imaging choice)

• 11 patients (0.4%) had high risk diagnoses with complications during first 30 days after randomization, with no significant difference among the 3 groups

• no difference when stratified by patients with a history of nephrolithiasis

• no significant difference among groups in the number of patients with serious adverse events; total of 466 SAE in 316 patients (91.4% were hospitalizations during f/u period; 26.4% involved surgical treatment of complications of nephrolithiasis)

• 5 reported deaths (occurred between 38 and 174 days after randomization) — none thought to be related to study participation

• the proportion of patients with a confirmed stone diagnosis within 6 months was similar in all 3 groups (POCUS 34.5% vs. US 31.2% vs. 32.7% CT)

• diagnostic accuracy based on result of initial imaging modality

  • POCUS          sensitivity 54% [48 - 60]; specificity 71% [67 - 75]

  • US                   sensitivity 57% [51 - 64]; specificity 73% [69 - 77]

  • CT                   sensitivity 88% [84 - 92]; specificity 58% [55 - 62]

Interpretation

• The US group was exposed to less radiation than the CT group and had no significant differences in the incidence of high-risk diagnoses with complications, total serious adverse events, or related serious adverse events.

• There also were no significant differences in pain scores, hospitalizations, ED readmissions among the groups.

• Many patients in the ultrasound groups did get additional imaging, but this was not the majority.

• Patients with a history of nephrolithiasis were less likely to undergo additional imaging with CT if they already had an ultrasound first (31% vs 36%). They did not have poorer outcomes than patients without a history of nephrolithiasis.

• Patients only undergoing POCUS and no other testing had a significantly shorter ED stay (1.3 hours)

• It is safe to pursue ultrasound as the initial imaging of choice for suspected nephrolithiasis (with additional imaging ordered as necessary at clinical discretion), though it should not necessarily be the only testing performed.

Strengths

• large size, diversity in ED settings, randomized design, assessment of clinically important outcomes, a high follow-up rate

Weaknesses

• no blinding of investigators, physicians, or patients as this was a pragmatic trial design

• independent review was used to characterize serious adverse events related to study participation

• strict reference standard for stone diagnosis which was unbiased, but prone to error based on the patient’s memory of self-reporting of stone passage

Internal/external validity

• Given the aforementioned strengths of this study and its pragmatic design, these findings appear both internally and externally valid and may be applied to daily clinical practice

Take-Home Points

What is your initial imaging test of choice, ultrasound (US) or non-contrast CT, and why?

• Ultrasound is a good choice for initial imaging as most patients do not end up requiring additional imaging during their visit. This leads to reduced cumulative radiation exposure.

Would you be satisfied with only US and no follow-up CT?

• In this study, 40.7% of those in the POCUS group and 27% in the formal ultrasound group underwent subsequent CT. Follow up CT should depend on the patient and ultrasound operator. Keep in mind that this study excluded patients with kidney disease, pregnant patients, and obese patients. They also excluded patients who were high risk for other pelvic and abdominal diseases. Lastly the POCUS operators were ED physicians with training “recommended by ACEP.”

Would you be confident in a point-of-care-ultrasound evaluation compared to a formal ultrasound?

• Yes. Sensitivity and specificity between these groups were similar.

Do outcomes for patients with suspected nephrolithiasis differ based on the initial imaging?

• No. There was no significant difference in subsequent adverse events, pain, return visits or hospitalizations, or delayed diagnoses of other serious conditions.

Should your medical decision-making change if the patient has a history of nephrolithiasis?

• In this study, patients with a history of nephrolithiasis were less likely to undergo additional imaging with CT if they already had an ultrasound first. They did not have poorer outcomes than patients without a history of nephrolithiasis. This suggests that it is safe to avoid ordering a CT in patients with recurrent stones.

What would you do if the same patient presented again with persistent pain from a previously diagnosed stone?

• The majority of patients with adverse outcomes were due to infectious causes. Consider alternative diagnoses such as pyelonephritis. Additionally, although rare, renal infarct can present with acute flank pain and is diagnosed with a contrast CT.

References

1. Fwu, C. W., Eggers, P. W., Kimmel, P. L., Kusek, J. W., & Kirkali, Z. (2013). Emergency department visits, use of imaging, and drugs for urolithiasis have increased in the United States. Kidney international, 83(3), 479-486.

2. Coursey, C. A., Casalino, D. D., Remer, E. M., Arellano, R. S., Bishoff, J. T., Dighe, M., ... & Leyendecker, J. R. (2012). ACR Appropriateness Criteria® acute onset flank pain–suspicion of stone disease. Ultrasound quarterly, 28(3), 227-233.

3. Smith-Bindman, R., Aubin, C., Bailitz, J., Bengiamin, R. N., Camargo Jr, C. A., Corbo, J., ... & Kang, T. L. (2014). Ultrasonography versus computed tomography for suspected nephrolithiasis. New England Journal of Medicine, 371(12), 1100-1110.

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Expert Commentary

Thank you very much to Dr.’s Ughreja and Akhetuamhen for an excellent blog post on a very relevant clinical topic.  This is a great summary of the landmark randomized trial published in NEJM in 2014 assessing CT vs two types of US for patients with suspected renal colic in the ED setting.  It is worth mentioning that this study was a multicenter study based in the US with representation from ED, Radiology, and Urology.  The above study was well summarized and bears repeating that, in this multicenter randomized study assessing CT vs POCUS vs radiology performed US in patients with suspected renal colic in the ED setting, initial US reduced radiation exposure without adversely affecting patient-centered outcomes.  It is worth mentioning several additional considerations and placing emphasis on others elucidated from this journal club review.

First, a subsequent systematic review (1) incorporating multispecialty (ED, Radiology, Urology) expert panel consensus recommendations has reiterated that in younger patients without a high suspicion for alternative diagnoses or complicating features of nephroureterolithiasis (such as fever, pyelonephritis, solitary kidney, dialysis, etc), US should be the initial diagnostic imaging modality of choice, if any.  It's a great paper, worth reading (and appreciating who the authors are), and worth recalling for bedside teaching to junior learners in the ED. 

Additionally, this paper brings to mind my second point, and something that is worth shouting from the hilltops -- a kidney stone is a clinical diagnosis!  Now, of course, this is exclusive of those patients with high-risk or complicating features (e.g. pediatrics, pregnancy, solitary kidney, fever, unstable/critically ill, unrelenting pain, atypical features, etc).  You don’t need any imaging to tell you the diagnosis in the vast majority of patients.  US or CT are helpful in confirming the diagnosis when there is uncertainty or non-trivial pretest probability of alternative diagnoses, excluding alternative diagnoses, and identifying exact stone location and size, which can be used to help counsel patients at the bedside regarding the anticipated clinical course and next steps in management. 

 Third, for those with proper training, and with some exceptions (see the systematic review paper for case vignettes that highlight these), POCUS is non-inferior to radiology-performed US.  And, it's not a “formal” US.  I can’t remember the last time I attended a black-tie ultrasonography session, but that's just me. 

 Fourth, it's worth mentioning that although CT use can lead to the identification of incidental findings more commonly than US, identification of these incidental findings still happens rather often with POCUS (a common example is a renal cyst).  Please ensure that you document and discuss with the patient accordingly.

 Finally, a burden on us as EM clinicians is training in and awareness of clinical practice guidelines and recommendations from specialties outside of EM.  As it relates to the diagnostic evaluation of suspected renal colic in the ED setting, the Choosing Wisely recommendations endorsed by the AUA are worth perusing as are the European/EUA guidelines, both of which suggest US as the initial diagnostic imaging modality of choice, for pediatric (CW) and non-high-risk patients without complicating features (EUA).

The bottom line is that CT is helpful for older patients or those in whom you are less sure about the diagnosis of renal colic.  For younger or low-risk patients, suspected renal colic is a clinical diagnosis and often needs no imaging, but ultrasound would be an evidence-based first step.  Thanks again toDr.’s Ughreja and Akhetuamhen.

References

1) Moore et al. Imaging in suspected renal colic: a systematic review of the literature and multispecialty consensus. J Urol 2019. 202(3):475-483.

Tim Loftus, MD, MBA

Assistant Professor of Emergency Medicine

Fellowship Director of the Clinical Operations and Administration Fellowship Program, Northwestern Department of Emergency Medicine

Medical Director of Emergency Services Northwestern Lake Forest Hospital and Grayslake Emergency Center

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Ughreja, K. Akhentuamhen, A. (2022, May 16). Journal Club: Ultrasonography versus Computed Tomography for Suspected Nephrolithiasis. [NUEM Blog. Expert Commentary by Loftus, T]. Retrieved from http://www.nuemblog.com/blog/nephrolithiasis-ultrasonography-versus-computed-tomography.

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Contrast Allergies for the Emergency Medicine Physician

Written by: Niki Patel, MD (NUEM ‘22) Edited by: Jesus Trevino (NUEM ‘19) Expert Commentary by: Seth Trueger, MD, MPH

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Expert Commentary

Thank you for this nice review. The main points I try to keep in mind is that contrast reactions are rare; they are rarely severe; and if a patient did not have a prior severe reaction (especially with pretreatment), it is very unlikely that they will have a severe reaction. Pretreatment probably does little but there are only so many hills to die on and most radiology departments won’t let us completely forego pretreatment. The key is working politely with the radiologists & techs to advocate for the patient and what they need (and if that means a consent form or removing a spurious allergy from the EHR, sure).

In my experience, institutional guideline are generally taken directly from the ACR guidelines (which is the point of specialty guidelines!) and therefore means ED patients need, at most, 4 hour prep; and anyone who hasn’t had a serious airway or anaphylactic reaction can probably be safely scanned with pretreatment as the potential benefit of the scan is higher than the potential risk of a reaction. Any scan that can wait for an 8 or 13 hour prep can be ordered by the admitting team (although I will get the pretreatment ball rolling to help them out). Occasionally a patient needs a scan so urgently they can get immediate doses of steroids and antihistamines and scanned immediately, and with proper SDM & documented consent, we can usually make this happen.

For preps, I try to document all the timing as clearly as possible because shifts change (docs, RNs, radiology techs, etc) and will usually put it clearly in the note & trackboard:

• 0730 methylpred 40mg IV

• 1030 diphenhydramine 50mg IV

• 1130 methylpred 40mg IV + CTPE

In my experience, communicating clearly with everyone involved as to what the plan is is the best way to ensure the plan gets carried out.

And lastly, there is no relation between seafood allergies and contrast allergies; you can’t be allergic to “iodine” (although that is fine as shorthand in the EHR to document a reaction); and there is no cross-allergy between topical povidine-iodine irritation and iodinated contrast (don’t ask).

Seth Trueger, MD, MPH

Assistant Professor of Emergency Medicine

Department of Emergency Medicine

Northwestern University expert commentator

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How To Cite This Post:

[Peer-Reviewed, Web Publication] Patel, N. Trevino, J. (2020, Aug 10). Contrast Allergies for the Emergency Medicine Physician. [NUEM Blog. Expert Commentary by Treuger, S]. Retrieved from http://www.nuemblog.com/blog/contrast-allergies-for-the-em-physician.

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Emergency Guide to Stroke Neuroimaging

Written by: Justin Seltzer, MD (PGY-3) Edited by: Luke Neill, MD (PGY-4) Expert commentary by: Babak Jahromi, MD, PhD

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According to the CDC, an ischemic stroke occurs approximately every 40 seconds in the US, with nearly 800,000 documented cases annually.[1] This, combined with an effective national stroke symptom public education program, has resulted in a large number of patients presenting to emergency departments for evaluation of stroke or stroke-like symptoms. Essential to this initial evaluation is neuroimaging, which in the emergency department is mainly CT based. 

However, despite frequent use, many emergency physicians are not familiar enough with stroke imaging to interpret images on their own. A prior post addressed the basics of reading a complete head CT, which you can find here. The goal of this article is to discuss the indications and limitations as well as to provide a basic guide to interpretation of noncontrast CT imaging of the brain (NCCT), CT angiography (CTA) of the head and neck, and CT perfusion (CTP) imaging in acute stroke evaluation.

Acute stroke imaging is obtained in the emergency department for two purposes. 

1. To evaluate rapidly for thrombolysis contraindications like hemorrhage and certain pathology such as vascular malformations and aneurysms. Thrombolysis has a high therapeutic benefit in stroke patients, with a number needed to treat of 10 within 3 hours of symptom onset and less than 20 if administered within 4.5 hours.[2,3] In addition, door to needle time of less than one hour is an established benchmark and quality measure.[3]

2. To identify a causative vascular lesion, which may or may not be amenable or contraindicatory to thrombolysis

Non-Contrast Head CT

NCCT is usually the first imaging modality obtained in the acute evaluation for stroke. Within the thrombolysis window (<4.5 hours), however, this scan is far more likely to detect hemorrhage than infarction. Chalela, et al., reviewed 356 patients evaluated for stroke symptoms at a single center over 18 months. They showed a sensitivity of 89% for detection of acute intracranial hemorrhage; conversely, the sensitivity for ischemic strokes less than 3 hours old was 12%, 16% for those older than 12 hours, and an overall sensitivity of 16%.[4] These findings are consistent with other studies and highlights the limitations of NCCT in acute stroke imaging. 

Despite the poor sensitivity for acute infarction, there are a few ways to improve detection. Windowing adjustments can enhance grey-white matter differentiation, as loss of this in an area anatomically associated with the presenting deficit is suggestive of acute infarction. A window width and center of approximately 50 each achieves adequate grey-white differentiation (Figure 1). Additionally, asymmetric, hyperdense section of cerebral vasculature, known as the “dense vessel” sign, is also highly suggestive of middle cerebral artery (MCA) occlusion.[5] As a side note, IV contrast should not be used outside of angiography to “enhance” the image as it may extravasate into the ischemic parenchyma mimicking hemorrhage.[6] 

Figure 1. NCCT of the brain in an acute right M1 occlusion with a last known well time was approximately 13 hours before. Windowing set at C50/W50 for improved grey-white differentiation. Official read: “A diffuse asymmetric hypodensity and subtle loss of gray-white matter differentiation in the right frontal and parietal region is highly concerning for an acute right MCA stroke.”

CT Angiography of the Head and Neck

The role of CTA in acute stroke evaluation is to identify the culprit vascular lesion and is an excellent addition to the emergent evaluation of acute ischemic stroke. A 2014 pooled analysis of 21 studies from 1993 to 2013 showed CTA has a sensitivity of 83.2% and specificity of 95% with a 97.1% negative predictive value for greater than 50% cerebral vascular stenosis;[7] a 2017 pooled analysis of 7 studies from 2003 to 2012 broadly reported a sensitivity of 93% and specificity of 100% for acute ischemic stroke.[8] CTA of the neck is also obtained to evaluate the contributing cervical vasculature. Since interpretation of angiography is dependent on knowledge of the relevant anatomy, the key structures are reviewed below. If a more detailed review is desired or necessary, several neuroanatomy texts may be found in the references. 

The major cerebral vasculature is supplied by the bilateral internal carotid arteries (ICA; “anterior circulation”) and the paired vertebral arteries (VA) that merge to form the basilar artery (BA; “posterior circulation”). The anterior circulation dominates perfusion of the cerebral hemispheres apart from the occipital lobe. The posterior circulation feeds the remaining structures, mainly the occipital lobe, cerebellum, and brain stem. 

Figure 2. CTA of the neck showing bilateral patent CCAs and VAs.

Anterior circulation

The anterior circulation starts with the ICA, which branches from the common carotid artery (CCA) in the upper neck at around the level of the fourth cervical vertebra. (Figures 2, 3). The ICA has four parts with seven defined segments; in general, segments assist with lesion localization and are provided in parenthesis. The cervical part (cervical segment, C1) is first and enters the skull at the carotid foramen (Figure 5). It is distinguished from its companion external carotid artery by a lack of extracranial branching. Once in the skull, the petrous part (petrous segment, C2) traverses the carotid canal within the petrous portion of the temporal bone (Figure 5). Moving out of the temporal bone, the ICA then crosses into the cavernous sinus, where it is known as the cavernous part (lacerum segment, C3, cavernous segment, C4, clinoid segment, C5). Navigating the bony turns in this area results in a characteristic curvature known as the “carotid siphon” (Figure 6). From here, the vessel passes through the dura, where it becomes the cerebral or supraclinoid part (ophthalmic segment, C6, communicating segment, C7) and gives off the ophthalmic, posterior communicating, and anterior choroidal arteries; these posterior communicating arteries (PCommA) run to the ipsilateral posterior cerebral arteries (PCA), thus connecting the anterior and posterior circulations and forming part of the circle of Willis (Figure 7). At the terminus, the internal carotid arteries bifurcate into the bilateral anterior cerebral arteries (ACA) and MCAs. Acute ICA lesions can cause dramatic symptoms due to restricted blood flow to the ipsilateral ACA and MCA and are large vessel occlusions.[9-12]

Figure 3. CTA of the neck showing the bilateral carotid bifurcations. Artifact from metal in the patient’s teeth.

Figure 4. CTA of the neck showing patent bilateral ICAs as well the the bilateral VAs entering the foramen magnum

The ACAs run between the frontal hemispheres in the longitudinal fissure and supply a large portion of the medial cerebral structures such as the medial frontal and parietal lobes as well as the basal ganglia and parts of the internal capsule. They are smaller than the MCAs and their course is recurrent frontal-occipital and inferior-superior, which can make visualization in the axial plane difficult to appreciate. The paired arteries are connected by the anterior communicating artery (ACommA) early in their course which is the final connection completing the circle of Willis (Figure 7). Lesions within the A1 segment, which runs from the carotid terminus to the ACommA are considered large vessel occlusions though may be better tolerated due to collateral flow through the anterior communicating artery.[9,10,12] 

Figure 5. CTA of the head showing the ICAs as they enter the skull and traverse the petrous portion of the temporal bone.

Figure 6. CTA of the head showing the ICA as it traverses the cavernous sinus; the carotid siphon is well visualized on the left.

The MCAs provide circulation to the remaining frontal and parietal lobes, basal ganglia, and internal capsules, as well as portions of the temporal lobes. They are larger and therefore more easily visualized than the ACAs (Figure 7). A lesion of the M1 segment, which runs from the carotid terminus to the bifurcation into the M2 segments, is considered a large vessel occlusion (Figures 8, 9).[9,10,12] 

Figure 7. CTA of the head showing an intact circle of Willis

Figure 8. CTA of the head showing an acute right M1 occlusion in the axial plane

Figure 9. Coronal MIPS of the same vascular occlusion noted in Figure 8 with clear deficit on the right compared with the left.

Posterior circulation

The posterior circulation starts with the VAs, which are subclavian branches that traverse the cervical spine via transverse foramina (Figures 2, 3). Prior to joining, each vertebral artery gives off an ipsilateral posterior inferior cerebellar arteries (PICA) as well as the contributing vessels that form the anterior and posterior spinal arteries. Upon entering the skull via the foramen magnum, the bilateral vertebral arteries join to form the basilar artery at about the level of the medullo-pontine junction (Figures 4, 5, 6). As the basilar artery moves superiorly it gives off the bilateral anterior inferior cerebellar arteries (AICA), multiple bilateral small perforating pontine arteries, the bilateral superior cerebellar arteries, and then finally terminates with a bifurcation into the bilateral posterior cerebral arteries (PCA). As noted prior, these PCAs connect with the ipsilateral posterior communicating arteries from the anterior circulation (Figure 7). Vertebral, basilar, and early posterior cerebral artery occlusions are considered large vessel occlusions but there is, as of now, limited data on mechanical thrombectomy in these territories.[9,10,12,13]

Application

Reading the scan itself is fairly straightforward based on the vascular anatomy. We recommend starting caudally (usually the aortic arch) in the axial plane and tracing all four cervical vessels cranially until they form the circle of Willis and from there extend out into the major branches. The coronal plane is particularly useful for evaluation of the anterior cervical vessels and the MCAs. Significant asymmetry or loss of contrast opacification in vascular beds anatomically consistent with the presenting symptoms should be considered strokes until proven otherwise. Make note of vascular abnormalities such as significant carotid stenosis, aneurysms, and malformations. 

Additional 2-D and 3-D post-processing images may also be provided. The most common is maximum intensity projection (MIP), which highlights high density structures over low density; this allows for improved visualization of the contrast enhanced vasculature at the expense of the surrounding brain tissue. However, MIP images can be falsely negative and should not be used alone for primary vascular evaluation.[14]

CT Perfusion

Though less common than CTA, CTP may also be acquired in the emergency setting to evaluate for territorial changes in cerebral blood flow suggestive of stroke. It is particularly valuable for identifying core infarct and salvageable ischemic penumbra and is becoming an important part of interventional decision making. It has a similar sensitivity and specificity for acute ischemic stroke as CTA, its use has been validated in multiple interventional stroke studies, and it has been shown to predict core infarct size accurately compared to the gold standard MRI.[7,8,15]

Basic concepts

While the specifics of CTP are complex and beyond the scope of this article, there are a few important concepts. CTP operates under the “central volume principle,” which is represented by the equation CBF = CBV/MTT and defines the relationship between cerebral blood volume (CBV; volume of flowing blood in a set volume of brain tissue), blood flow (CBF; per time unit rate of flowing blood in a set volume of brain tissue), and mean transit time (MTT;  average time for blood to transit a set volume of brain tissue). To illustrate this concept, imagine an acute arterial occlusion. The obstruction causes an immediate increase in MTT due to slowed arterial flow through the affected tissue. To maintain CBF a local compensatory vasodilation occurs, increasing CBV. However, this vasodilation may not be able to compensate for rising MTT, causing a progressively inadequate CBF that may result in infarction.[5,16]

Algorithms translate detected changes in MTT, CBV, and CBF into images that can be used in clinical decision-making. MTT is obtained by measuring the movement of contrast through the affected tissue; this also gives a value known as Tmax, which is the time to achieve peak contrast density. CBV and CBF are calculated relative values (rCBF, rCBV) and based off of the surrounding normal tissue. Composite metrics, such as mismatch ratio, the ratio of penumbra to the core infarct volumes, and mismatch volume, the penumbra volume minus the core infarct volume, are also generated.[11] Though there is no set rule, there is evidence that thrombolysis benefit is maximized and hemorrhage risk minimized with a mismatch ratio of 1.8 or greater, a mismatch volume of 15ml or greater, and a core infarct volume less than 70ml.[17]

Figure 10. Illustrative CTP report for the same acute right M1 occlusion from Figures 8 and 9 showing the core infarct (purple) and associated penumbra (green). Note the large mismatch volume and ratio, indicating a relatively small core infarct relative to the threatened penumbra.

Application

These values are then made into “parametric maps” superimposed onto axial CT slices, allowing for visual identification (Figures 10, 11). Different software may present the values and parametric maps differently; note that our institution uses RAPID (iSchemaView, Menlo Park, CA) and our example figures were generated by this software. Using Figure 10 as an example, we see purple and green areas as well as different volumes and ratios. The purple area corresponds to the volume of tissue with a rCBF less than 30% of the unaffected, healthy tissue and is considered the core infarct area. The green area corresponds to the volume of tissue with a Tmax longer than six seconds and is considered the ischemic penumbra. Though these threshold values were used and validated by the SWIFT PRIME and EXTEND-IA trials, they are not definitive or universal.[15,18] Familiarization with an institution’s software and threshold values is vital to interpreting CTP properly.

Importantly, CTP can be abnormal in other situations such as with chronic infarcts, vasospasm from subarachnoid hemorrhage, microvascular ischemia, and cerebral changes associated with seizure and feeding vessel stenosis.[16] Always interpret CTP in the context of the other imaging findings and anatomic consistency. 

Figure 11. Illustrative CTP report for the same acute right M1 occlusion from Figured 8, 9, and 10 showing territorially increased MTT with subtle reduction in CBF and a small area of asymmetrically elevated CBV in the area corresponding to infarction in Figure 10. This figure visually highlights the relationships between rCBV, cCBF, MTT, and Tmax.

Take Away Points

CT is the primary source of neuroimaging in the emergency department evaluation of stroke patients. NCCT is poor at detecting early acute infarcts directly, however it is excellent for hemorrhage detection. Use of CTA can demonstrate causative vascular lesions and addition of CTP can further delineate ischemia and determine how amenable it might be to intervention. Not all lesions identified by CTA and CTP will be amenable to thrombolysis or thrombectomy, but these are usually the only time effective ways available to emergency physicians to identify those that might be. Educating emergency physicians about these imaging modalities can both improve patient care through more rapid diagnosis in suspected stroke cases as well as help to streamline communication and treatment planning with consulting neurologists and neurointerventionalists. 

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Expert Commentary

This is a well-written synopsis of modern neuroimaging used today’s ED for workup and emergent treatment of acute stroke. The reader should keep in mind that the primary thrust of this blog segment is on acute ischemic stroke - while advanced CT imaging (i.e. CTA) also has a crucial role in hemorrhagic stroke, this is more thoroughly addressed elsewhere.

Practically speaking, today’s CT/CTP/CTA is to suspected stroke what an EKG is to chest pain in the ED. While confirmatory tests (MRI for stroke, troponin for MI) take more time, all actionable data depends on the initial CT/CTP/CTA in acute stroke. I would also categorize the purpose of acute stroke imaging in the ED into two categories, but with perhaps broader brush-strokes:

1. Determine if stroke is ischemic or hemorrhagic (“blood or no blood on CT”), and

2. Determine the next course of action:

   1. If ischemic, do temporal and anatomic criteria mandate IV tPA, endovascular thrombectomy, both, or neither, 

   2. If hemorrhagic, is there mass effect and/or an underlying vascular lesion (arterial or venous) that mandates urgent intervention beyond best medical care.

While NCCT is sufficient to determine whether to proceed with IV tPA in the 0-4.5 hour time-window (with an NNT of 10-20), CTP/CTA are key to determining whether the patient requires emergent endovascular thrombectomy in the 0-24 hour time-window (with an NNT of 2.6-4). As these two time-windows overlap, the most practical approach is increasingly to obtain multi-modality imaging up-front / as rapidly as possible in the ED. It is important to remember that as of 2015, both IV tPA and endovascular thrombectomy are considered standard-of-care, and any patient presenting with acute ischemic stroke must undergo full workup and consideration of both treatments based upon national society / consensus guidelines.

An added note on NCCT versus CTP: while NCCT is the oldest modality in the ED, it continues to have tremendous value in acute stroke imaging. Presence or absence of early stroke changes on NCCT (quantified by the ASPECT score) can at times trump CTP in the 0-6 hr time-window, and CTP within any time-window must be interpreted in context of NCCT findings. For example, CTP may show no abnormality (or even luxury perfusion) in an area of established stroke on NCCT in cases of spontaneous recanalization. On the other hand, CTP can be very helpful in detecting small areas of ischemia not well seen on CT/CTA (even when reading NCCT using optimized 35/35 or 40/40 “stroke windows”), and CTP has higher sensitivity for small/distal branch occlusions than either CT/CTA.

The approach to cerebrovascular arterial anatomy is nicely reviewed. A few additional comments:

1. ICA: acute ICA occlusions are most dramatic when reaching the terminus (thereby blocking the MCA/ACA), but those not reaching the supraclinoid ICA may at times be well-tolerated due to collaterals across the Circle of Willis,

2. VA: the course/anatomy of the VA is rather variable, with one VA (typically the right) being less dominant as we age; similarly, PICA can have a variable origin and territory of supply, and

3. BA: while randomized trials of endovascular thrombectomy for basilar occlusion have not been published, the natural history of BA occlusion is typically devastating/fatal, and a large body of non-randomized data (case series/cohorts) shows marked improvement over this natural history following endovascular thrombectomy for BA stroke in selected patients.

Vice Chair of Regional Neurosurgery

Professor of Neurological Surgery

Department of Neurological Surgery

Feinberg School of Medicine

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How to Cite this Post

[Peer-Reviewed, Web Publication] Seltzer J, Neill L. (2020, Jan 6). Emergency Guide to Stroke Neuroimaging. [NUEM Blog. Expert Commentary by Jahromi B]. Retrieved from http://www.nuemblog.com/blog/2018/4/20/stroke-neuroimaging

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